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| 1 | Disruption of the TWEAK/Fn14 pathway prevents 5-fluorouracil-induced diarrhea in mice显示文摘AIM To clarify the roles of TWEAK and its receptor Fn14 in 5-fluorouracil(5-FU)-induced diarrhea.METHODS Diarrhea was induced in wild-type(WT), Fn14 knockout(KO), and IL-13 receptor(IL-13R)α1 KO BALB/c mice using a single injection of 5-FU. Histological analysis, cytokine analysis, and flow cytometry was performed on ileal tissues and cells. Murine colon carcinomabearing mice were co-treated with an anti-TWEAK antibody and 5-FU. Embryonic fibroblast response to cytokines was also analyzed.RESULTS5-FU induced high Fn14 expression in epithelial cells. The severity of 5-FU-induced diarrhea was lower in Fn14 KO mice compared with WT mice. Administration of anti-TWEAK antibody reduced 5-FU-induced diarrhea without affecting the antitumor effects of 5-FU in vivo. 5-FU-induced expression of IL-13, IL-17 A, TNF-α, and IFN-γ in the ileum was Fn14 dependent. The severity of 5-FU-induced diarrhea was lower in IL-13Rα1 KO mice, indicating major role for IL-13 signaling via IL-13Rα1 in pathogenesis. We found that IL-13Rα2, an IL-13 neutralizing/cell protective receptor, was strongly induced by IL-33 in vitro and in vivo. IL-13Rα2 was upregulated in the ileum of 5-FU-treated Fn14 KO mice. Thus, the deletion of Fn14 upregulated IL-13Rα2 expression, which reduced IL-13 expression and activity. CONCLUSION Disruption of the TWEAK/Fn14 pathway affects several interconnected pathways, including those associated with IL-13, IL-33, and IL-13Rα2, to attenuate 5-FUinduced intestinal side effects. | Takuhito Sezaki Yuki Hirata Teruki Hagiwara Yuki I Kawamura Tadashi Okamura Rieko Takanashi Kenta Nakano Miwa Tamura-Nakano Linda C Burkly Taeko Dohi | 2017 | World Journal of Gastroenterology2017，23，13： | 3 |
| 2 | Treatment with humanized monocloneal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates显示文摘 | Krik AD Burkly LC Batty DS etal | 1999 | Nat Med1999，5，6： | 1 |
| 3 | Expression of relB is required for the development of thymic medulla and dendritic cells显示文摘 | Burkly L Hession L Ogata C | 1995 | Nature1995，373，： | 1 |
| 4 | Urinary TWEAK and the activity of lupus nephritis显示文摘 | Schwartz N Su L Burkly LC | 2006 | J Autoimmun2006，27，4： | 1 |
| 5 | Mobilization of CD34^+ haematopoietic stem cells is associated with a functional inactivation of the integrin very late antigen 4显示文摘 | Lichterfeld M Martin S Burkly L | 2000 | Br J Haematol2000，110，1： | 1 |
| 6 | TWEAK/Fnl4 inter- actions are instrumental in the pathogenesis of nephritis in the Chronic Graft-versus-Host model of systemic lupus ery- thematosus显示文摘 | Zhao Z Burkly L Campbell S | 2007 | J Immunol2007，179，11： | 1 |
| 7 | Expression of relB is required for the development of thymic medulla and dendritic cells显示文摘 | Burkly L Hession C Ogata L | 1995 | Nature1995，373，9： | 1 |
| 8 | TWEAK is a novel arthritogenic mediator 显示文摘 | Perper SJ Browning B Burkly LC | 2006 | J Immunol2006，177，4： | 1 |
| 9 | TWEAK is a novel arthritogenie mediator显示文摘 | Perper SJ Browning B Burkly LC | 2006 | Immunol2006，177，4： | 1 |
| 10 | Expression of relB is required for the development of thymic medulla and dendritic cells显示文摘 | BURKLY L HESSION C OGATA L | 1995 | Nature1995，373，9： | 1 |
| 11 | Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates显示文摘 | Kirk AD Burkly LC Batty DS | 1999 | Nat Med1999，5，6： | 1 |
| 12 | TNF-like weak inducer of apoptosis(TWEAK) induces inflammatory and proliferative effects in human kidney cells显示文摘 | Gao HX Campbell SR Burkly LC | 2009 | Cytokine2009，46，1： | 1 |
| 13 | TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus显示文摘 | Zhao Z Burkly LC Campbell S | 2007 | Immunol2007，179，11： | 1 |
| 14 | Urinary TWEAK and the activity of lupus nephritis显示文摘 | Schwartz N Su L Burkly LC | | 0，，04： | 1 |
| 15 | Urinary TWEAK and the activity of lupus nephritis显示文摘 | Schwartz N Su L Burkly LC | 2006 | Autoimmun2006，27，4： | 1 |
| 16 | TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus显示文摘 | Zhao Z Burkly LC Campbell S | | 0，，11： | 1 |
| 17 | Fnl4-Fe Fusion protein regulates atherosclerosis in ApoE -/- mice and inhibits macro- phage lipid uptake in vitro 显示文摘 | Schapira K Burkly LC Zheng TS | 2009 | Arterioscler Thromb Vasc Biol2009，29，12： | 1 |
| 18 | T-cell tolerance by clonal anergy in transgenic mice with nonlymphoid expression of MHC class Ⅱ I-E显示文摘 | Lo D Kanagawa O | 1989 | Nature1989，342，6249： | 1 |
| 19 | Urinary TWEAK as a biomarker of lupus nephritis:a multicenter cohort study显示文摘 | Schwartz N Rubinstein T Burkly LC | | 0，，05： | 1 |
| 20 | Clonal deletion of Vβ5^+ T ceils by transgenic I-E restricted to thymic medullary epithelium 显示文摘 | Burkly LC Degermann S Longley J | 1993 | J Immunol1993，151，： | 1 |
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