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| 1 | Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes显示文摘The objective was to investigate the effect of kinsenoside(Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis(OA) progression.RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction(q RT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium(CM) and IL-1β were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection(ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB(NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases(MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1β-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages,promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment. | Feng Zhou Jingtian Mei Xiuguo Han Hanjun Li Shengbing Yang Minqi Wang Linyang Chu Han Qiao Tingting Tang | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 35 |
| 2 | Paeoniflorin inhibits macrophage-mediated lung cancer metastasis显示文摘Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages(M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages(stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 μmol·L-1, P < 0.01 or P < 0.05 vs control group). Paeoniflorin could decrease the cell populations at S phases(paeoniflorin 10, 30, 100 μmol·L-1, P < 0.05 vs control group) and increase the cell populations at G0-G1 phases of Lewis lung cancer cells(paeoniflorin 100 μmol·L-1, P < 0.05 vs control group) and reduce the numbers of M2 macrophages in peritoneal macrophages induced by IL-4(paeoniflorin 1, 3, 10, 30, 100 μmol·L-1, P < 0.01 vs Control group). Paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo(paeoniflorin 20, 40 mg·kg-1, P < 0.01 vs control group). These results suggest that paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages. | WU Qi CHEN Gang-Ling LI Ya-Juan CHEN Yang LIN Fang-Zhen | 2015 | Chinese Journal of Natural Medicines2015，13，12： | 21 |
| 3 | Abdominal paracentesis drainage ameliorates severe acute pancreatitis in rats by regulating the polarization of peritoneal macrophages显示文摘AIM To investigate the role of peritoneal macrophage(PM) polarization in the therapeutic effect of abdominal paracentesis drainage(APD) on severe acute pancreatitis(SAP).METHODS SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot.RESULTS APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin(IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of proinflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats.CONCLUSION These findings suggest that APD treatment exerts antiinflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanism underlying its therapeutic effect. | Ruo-Hong Liu Yi Wen Hong-Yu Sun Chun-Yu Liu Yu-Fan Zhang Yi Yang Qi-Lin Huang Jia-Jia Tang Can-Chen Huang Li-Jun Tang | 2018 | World Journal of Gastroenterology2018，24，45： | 20 |
| 4 | The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?显示文摘Macrophages are one of the most abundant leukocyte populations infiltrating tumor tissues and can exhibit both tumoricidal and tumor-promoting activities.In 1989,we reported the purification of monocyte chemoattractant protein-1(MCP-1)from culture supernatants of mitogen-activated peripheral blood mononuclear cells and tumor cells.MCP-1 is a potent monocyte-attracting chemokine,identical to the previously described lymphocyte-derived chemotactic factor or tumor-derived chemotactic factor,and greatly contributes to the recruitment of blood monocytes into sites of inflammatory responses and tumors.Because in vitro-cultured tumor cells often produce significant amounts of MCP-1,tumor cells are considered to be the main source of MCP-1.However,various nontumor cells in the tumor stroma also produce MCP-1 in response to stimuli.Studies performed in vitro and in vivo have provided evidence that MCP-1 production in tumors is a consequence of complex interactions between tumor cells and non-tumor cells and that both tumor cells and non-tumor cells contribute to the production of MCP-1.Although MCP-1 production was once considered to be a part of host defense against tumors,it is now believed to regulate the vicious cycle between tumor cells and macrophages that promotes the progression of tumors. | Teizo Yoshimura | 2018 | Cellular & Molecular Immunology2018，15，4： | 19 |
| 5 | Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke显示文摘Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke.Microglial activation and polarization,and the inflammatory response mediated by these cells play important roles in the development,progression and outcome of brain injury after ischemic stroke.Currently,there is no effective strategy for treating ischemic stroke in clinical practice.Therefore,it is clinically important to study the role and regulation of microglia in stroke.In this review,we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke,with the aim of providing a better understanding of the relationship between ischemic stroke and microglia. | Wan Zhang Tian Tian Shao-Xin Gong Wen-Qian Huang Qin-Yi Zhou Ai-Ping Wang Ying Tian | 2021 | Neural Regeneration Research2021，16，1： | 17 |
| 6 | Role of macrophages in the progression of acute pancreatitis显示文摘In addition to pancreatic cells,other inflammatory cell populations contribute to the generation of inflammatory mediators during acute pancreatitis.In particular,macrophages could be activated by mediators released during pancreatitis by a damaged pancreas.It has been reported that peritoneal macrophages,alveolar macrophages and Kupffer cells become activated in different stages of severe acute pancreatitis.However,macrophages display remarkable plasticity and can change their physiology in response to environmental cues.Depending on their microenvironmental stimulation,macrophages could follow different activation pathways resulting in marked phenotypic heterogeneity.This ability has made these cells interesting therapeutical targets and several approaches have been assayed to modulate the progression of inflammatory response secondary to acute pancreatitis.However,despite the recent advances in the modulation of macrophage function in vivo,the therapeutical applications of these strategies require a better understanding of the regulation of gene expression in these cells. | Sabrina Gea-Sorlí Daniel Closa | 2010 | World Journal of Gastrointestinal Pharmacology and Therapeutics2010，1，5： | 16 |
| 7 | Targeting the tumor stroma in hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is one of the most common and deadly cancers worldwide. In ninety percent of the cases it develops as a result of chronic liver damage and it is thus a typical inflammationrelated cancer characterized by the close relation between the tumor microenvironment and tumor cells. The stromal environment consists out of several cell types, including hepatic stellate cells, macrophages and endothelial cells. They are not just active bystanders in the pathogenesis of HCC, but play an important and active role in tumor initiation, progression and metastasis. Furthermore, the tumor itself influences these cells to create a background that is beneficial for sustaining tumor growth. One of the key players is the hepatic stellate cell, which is activated during liver damage and differentiates towards a myofibroblast-like cell. Activated stellate cells are responsible for the deposition of extracellular matrix, increase the production of angiogenic factors and stimulate the recruitment of macrophages. The increase of angiogenic factors(which are secreted by macrophages, tumor cells and activated stellate cells) will induce the formation of new blood vessels, thereby supplying the tumor with more oxygen and nutrients, thus supporting tumor growth and offering a passageway in the circulatory system. In addition, the secretion of chemokines by the tumor cells leads to the recruitment of tumor associated macrophages. These tumor associated macrophages are key actors of cancer-related inflammation, being the main type of inflammatory cells infiltrating the tumor environment and exerting a tumor promoting effect by secreting growth factors, stimulating angiogenesis and influ-encing the activation of stellate cells. This complex interplay between the several cell types involved in liver cancer emphasizes the need for targeting the tumor stroma in HCC patients. | Femke Heindryckx Pär Gerwins | 2015 | World Journal of Hepatology2015，7，2： | 16 |
| 8 | Biological response to prosthetic debris显示文摘Joint arthroplasty had revolutionized the outcome of orthopaedic surgery. Extensive and collaborative work of many innovator surgeons had led to the development of durable bearing surfaces, yet no single material is considered absolutely perfect. Generation of wear debris from any part of the prosthesis is unavoidable. Implant loosening secondary to osteolysis is the most common mode of failure of arthroplasty. Osteolysis is the resultant of complex contribution of the generated wear debris and the mechanical instability of the prosthetic components. Roughly speaking, all orthopedic biomaterials may induce a universal biologic hostresponse to generated wear débris with little specific characteristics for each material; but some debris has been shown to be more cytotoxic than others. Prosthetic wear debris induces an extensive biological cascade of adverse cellular responses, where macrophages are the main cellular type involved in this hostile inflammatory process. Macrophages cause osteolysis indirectly by releasing numerous chemotactic inflammatory mediators, and directly by resorbing bone with their membrane microstructures. The bio-reactivity of wear particles depends on two major elements: particle characteristics(size, concentration and composition) and host characteristics. While any particle type may enhance hostile cellular reaction, cytological examination demonstrated that more than 70% of the debris burden is constituted of polyethylene particles. Comprehensive understanding of the intricate process of osteolysis is of utmost importance for future development of therapeutic modalities that may delay or prevent the disease progression. | Diana Bitar Javad Parvizi | 2015 | World Journal of Orthopedics2015，6，2： | 16 |
| 9 | Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches显示文摘A coordinated interaction between osteogenesis and osteoimmune microenvironment is essential for successful bone healing.In particular,macrophages play a central regulatory role in all stages of bone repair.Depending on the signals they sense,these highly plastic cells can mediate the host immune response against the exterior signals of molecular stimuli and implanted scaffolds,to exert regenerative potency to a varying extent.In this article,we first encapsulate the immunomodulatory functions of macrophages during bone regeneration into three aspects,as sweeper,mediator and instructor.We introduce the phagocytic role of macrophages in different bone healing periods(‘sweeper’)and overview a variety of paracrine cytokines released by macrophages either mediating cell mobilisation,vascularisation and matrix remodelling(‘mediator’),or directly driving the osteogenic differentiation of bone progenitors and bone repair(‘instructor’).Then,we systematically classify and discuss the emerging engineering strategies to recruit,activate and modulate the phenotype transition of macrophages,to exploit the power of endogenous macrophages to enhance the performance of engineered bone tissue. | Yiming Niu Zhenzhen Wang Yuchen Shi Lei Dong Chunming Wang | 2021 | Bioactive Materials2021，6，1： | 14 |
| 10 | Chitosan hydrogel incorporated with dental pulp stem cell-derived exosomes alleviates periodontitis in mice via a macrophage-dependent mechanism显示文摘Periodontitis is caused by host immune-inflammatory response to bacterial insult.A high proportion of proinflammatory macrophages to anti-inflammatory macrophages leads to the pathogenesis of periodontitis.As stem cell-derived exosomes can modulate macrophage phenotype,dental pulp stem cell-derived exosomes(DPSC-Exo)can effectively treat periodontitis.In this study,we demonstrated that DPSC-Exo-incorporated chitosan hydrogel(DPSC-Exo/CS)can accelerate the healing of alveolar bone and the periodontal epithelium in mice with periodontitis.Gene Ontology(GO)term enrichment analysis showed that treatment with DPSC-Exo/CS ameliorated periodontal lesion by suppressing periodontal inflammation and modulating the immune response.Specifically,DPSC-Exo/CS facilitated macrophages to convert from a pro-inflammatory phenotype to an anti-inflammatory phenotype in the periodontium of mice with periodontitis,the mechanism of which could be associated with miR-1246 in DPSC-Exo.These results not only shed light on the therapeutic mechanism of DPSCExo/CS but also provide the basis for developing an effective therapeutic approach for periodontitis. | Zongshan Shen Shuhong Kuang Yong Zhang Mingmei Yang Wei Qin Xuetao Shi Zhengmei Lin | 2020 | Bioactive Materials2020，5，4： | 14 |
| 11 | Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis显示文摘AIM To explore the role of macrophages in chronic pancreatitis(CP) and the effect of Dachaihu decoction(DCHD) on pancreatic fibrosis in mice.METHODS Kun Ming mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine(3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6(IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1(MCP-1), macrophage inflammatory protein-1α(MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas. RESULTS Compared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α m RNA, and fibronectin levels were reduced. CONCLUSION The dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas. | Li-Fang Duan Xiao-Fan Xu Lin-Jia Zhu Fang Liu Xiao-Qin Zhang Nan Wu Jian-Wei Fan Jia-Qi Xin Hong Zhang | 2017 | World Journal of Gastroenterology2017，23，40： | 12 |
| 12 | Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages显示文摘Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly.Exacerbating this issue,there are currently few drugs reported to effectively treat silicosis.Tetrandrine is the only drug approved for silicosis treatment in China,and despite more than decades of use,its efficacy and mechanisms of action remain largely unknown.Here,in this study,we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration.To this end,we used multiple cardiopulmonary function test,as well as markers for inflammation and fibrosis.Moreover,using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice,our results provide a novel description of the target pathways for tetrandrine.Specifically,we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages.Taken together,our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets.Our results also facilitated the wider adoption and development of tetrandirne,potentially accelerating a globally accepted therapeutic strategy for silicosis. | Mei-yue Song Jia-xin Wang You-liang Sun Zhi-fa Han Yi-tian Zhou Ying Liu Tian-hui Fan Zhao-guo Li Xian-mei Qi Ya Luo Pei-ran Yang Bai-cun Li Xin-ri Zhang Jing Wang Chen Wang | 2022 | Acta Pharmacologica Sinica2022，43，5： | 12 |
| 13 | Scavenger receptor BI: A multi-purpose player in cholesterol and steroid metabolism显示文摘Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function. | Menno Hoekstra Theo JC Van Berkel Miranda Van Eck | 2010 | World Journal of Gastroenterology2010，16，47： | 11 |
| 14 | Anti-inflammatory pathways and alcoholic liver disease: Role of an adiponectin/interleukin-10/heme oxygenase-1 pathway显示文摘The development of alcoholic liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. Enhanced inflammation in the liver during ethanol exposure is an important contributor to injury. Kupffer cells, the resident macrophages in liver, are particularly critical to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharide via Toll-like receptor 4. This sensitization enhances production of inflammatory mediators, such as tumor necrosis factor-α and reactive oxygen species, that contribute to hepatocyte dysfunction, necrosis, apoptosis, and fibrosis. Impaired resolution of the inflammatory process probably also contributes to ALD. The resolution of inflammation is an active, highly coordinated response that can potentially be manipulated via therapeutic interventions to treat chronic inflammatory diseases. Recent studies have identif ied an adiponectin/interleukin-10/heme oxygenase-1 (HO-1) pathway that is profoundly effective in dampening the enhanced activation of innate immune responses in primary cultures of Kupffer cells, as well as in an in vivo mouse model of chronic ethanol feeding. Importantly, induction of HO-1 also reduces ethanol-induced hepatocellular apoptosis in this in vivo model. Based on these data, we hypothesize that the development of therapeutic agents to regulate HO-1 and its downstream targets could be useful in enhancing the resolution of inflammation during ALD and preventing progression of early stages of liver injury. | Palash Mandal Michele T Pritchard Laura E Nagy | 2010 | World Journal of Gastroenterology2010，16，11： | 11 |
| 15 | The prognostic impact of traditional Chinese medicine monomers on tumor-associated macrophages in non-small cell lung cancer显示文摘Non-small cell lung cancer(NSCLC) accounts for 80%-85% of all lung malignancies and good diagnosis and prognosis of NSCLC are critical to the increase of its survival rate. Tumor-associated macrophages(TAM) abundantly present in numerous cancer types, and the role of TAMs in tumor biology and their prognostic value in cancer become major topics of interest. After various stimulations in the tumor microenvironment, TAMs develop into a M1(tumor-inhibitory) phenotype or M2(tumor-promoting) phenotype. Recent studies show that traditional Chinese medicine(TCM) monomers have markedly inhibitory actions for NSCLC through M1/M2 modulation. Due to the TCM monomers mainly covered five categories, i.e. terpenoids, flavonoids, polysaccharides, natural polyphenols, and alkaloids. Thus, we will discuss the regulation of TCM monomers on TAM involve in these five parts in this review. In addition, the potential role of TAMs as therapeutic targets will be discussed. | WAN Liang-Qin TAN Yan JIANG Miao HUA Qian | 2019 | Chinese Journal of Natural Medicines2019，17，10： | 11 |
| 16 | Inflammatory status in human hepatic cirrhosis显示文摘This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus(HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcoholinduced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis(HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared withHCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gutmesenteric lymph nodes-peritoneal-systemic axis. | María Martínez-Esparza María Tristán-Manzano Antonio J Ruiz-Alcaraz Pilar García-Penarrubia | 2015 | World Journal of Gastroenterology2015，21，41： | 10 |
| 17 | Role of pro-and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity显示文摘In obesity, persistent low-grade inflammation is considered as a major contributor towards the progression to insulin resistance and type 2 diabetes while in lean subjects the immune environment is non-inflammatory. Massive adipose tissue(AT) infiltration by pro-inflammatory M1 macrophages and several T cell subsets as obesity develops leads to the accumulation-both in the AT and systemically-of numerous pro-inflammatory cytokines, including interleukin-1β(IL-1β), tumor necrosis factor a, IL-17 and IL-6 which are strongly associated with the progression of the obese phenotype towards the metabolic syndrome. At the same time, anti-inflammatory M2 macrophages and Th subsets producing the antiinflammatory cytokines IL-10, IL-5 and interferon-γ, including Th2 and T-reg cells are correlated to the maintenance of AT homeostasis in lean individuals. Here, we discuss the basic principles in the control of the interaction between the AT and infiltrating immune cells both in the lean and the obese condition with a special emphasis on the contribution of pro-and antiinflammatory cytokines to the establishment of the insulinresistant state. In this context, we will discuss the current knowledge about alterations in the levels on pro-and antiinflammatory cytokines in obesity, insulin resistance and type 2 diabetes mellitus, in humans and animal models. Finally, we also briefly survey the recent novel therapeutic strategies that attempt to alleviate or reverse insulin resistance and type 2 diabetes via the administration of recombinant inhibitory antibodies directed towards some pro-inflammatory cytokines. | Luciano Pirola JoséCandido Ferraz | 2017 | World Journal of Biological Chemistry2017，8，2： | 10 |
| 18 | Pancreatic and pulmonary mast cells activation during experimental acute pancreatitis显示文摘AIM:To study the activation of pancreatic and pulmonary mast cells and the effect of mast cell inhibition on the activation of peritoneal and alveolar macrophages during acute pancreatitis.METHODS:Pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats.The mast cell inhibitor cromolyn was administered intraperitoneally(i.p.) 30 min before pancreatitis induction.The pancreatic and pulmonary tissue damage was evaluated histologically and mast cells and their state of activation were evaluated.Peritoneal and alveolar macrophages were obtained and the expression of tumor necrosis factor α was determined.Myeloperoxidase activity was measured to evaluate the effect of mast cell inhibition on the progression of the inflammatory process.Finally,the effect of plasma on cultured mast cells or macrophages was evaluated in vitro.RESULTS:The mast cell stabilizer signif icantly reduced inflammation in the pancreas and lung and the activation of alveolar macrophages but had no effect on peritoneal macrophages.Mast cell degranulation was observed in the pancreas during pancreatitis but no changes were observed in the lung.Plasma from rats with pancreatitis could activate alveolar macrophages but did not induce degranulation of mast cells in vitro.CONCLUSION:Pancreatic mast cells play an important role in triggering the local and systemic inflammatory response in the early stages of acute pancreatitis.In contrast,lung mast cells are not directly involved in the inflammatory response related to pancreatic damage. | Inmaculada Lopez-Font Sabrina Gea-Sorlí Enrique de-Madaria Luis M Gutiérrez Miguel Pérez-Mateo Daniel Closa | 2010 | World Journal of Gastroenterology2010，16，27： | 10 |
| 19 | Salidroside Inhibits Lipopolysaccharide-ethanol-induced Activation of Proinflammatory Macrophages via Notch Signaling Pathway显示文摘Activation of macrophages is a key event for the pathogenesis of various inflammatory diseases.Notch signaling pathway recently has been found to be a critical pathway in the activation of proinflammatory macrophages.Salidroside (Sal),one of main bioactive components in Rhodiola crenulata (Hook.F.et Thoms) H.ohba,reportedly possesses anti-inflammatory activity and ameliorates inflammation in alcohol-induced hepatic injury.However,whether Sal regulates the activation of proinflammatory macrophages through Notch signaling pathway remains unknown.The present study investigated the effects of Sal on macrophage activation and its possible mechanisms by using both alcohol and lipopolysaccharide (LPS) to mimic the microenvironment of alcoholic liver.Detection of THP-1-derived macrophages exhibited that Sal could significantly decrease the expression of tumor necrosis factor-α(TNF-α),interleukinbeta (IL-1β)and IL-6 in the macrophages at both mRNA and protein levels.Furthermore,Sal significantly suppressed NF-kB activation via Notch-Hes signaling pathway in a dose-dependent manner.Moreover,in the microenvironment of alcoholic liver,the expression of Notch-dependent pyruvate dehydrogenase phosphatase 1 (PDP1) was elevated,and that of Ml gene expression [inducible NO synthase (NOS2)] was up-regulated.These changes could all be effectively ameliorated by Sal.The aforementioned findings demonstrated that Sal could inhibit LPS-ethanol-induced activation of proinflammatory macrophages via Notch signaling pathway. | Jian-sha LI Lu-yao FAN Meng-dan YUAN Ming-you XING | 2019 | Current Medical Science2019，39，4： | 10 |
| 20 | Macrophages and the maintenance of homeostasis显示文摘There have been many chapters written about macrophage polarization.These chapters generally focus on the role of macrophages in orchestrating immune responses by highlighting the T-cell-derived cytokines that shape these polarizing responses.This bias toward immunity is understandable,given the importance of macrophages to host defense.However,macrophages are ubiquitous and are involved in many different cellular processes,and describing them as immune cells is undoubtedly an oversimplification.It disregards their important roles in development,tissue remodeling,wound healing,angiogenesis,and metabolism,to name just a few processes.In this chapter,we propose that macrophages function as transducers in the body.According to Wikipedia,WA transducer is a device that converts energy from one form to another.^The word transducer is a term used to describe both the'sensor,which can interpret a wide range of energy forms,and the'actuator,which can switch voltages or currents to affect the environment.Macrophages are able to sense a seemingly endless variety of inputs from their environment and transduce these inputs into a variety of different response outcomes.Thus,rather than functioning as immune cells,they should be considered more broadly as cellular transducers that interpret microenvironmental changes and actuate vital tissue responses.In this chapter,we will describe some of the sensory stimuli that macrophages perceive and the responses they make to these stimuli to achieve their prime directive,which is the maintenance of homeostasis. | David M.Mosser Kajal Hamidzadeh Ricardo Goncalves | 2021 | Cellular & Molecular Immunology2021，18，3： | 10 |
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