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Your search keyword '"Tumor Necrosis Factor Ligand Superfamily Member 15 antagonists & inhibitors"' showing total 2 results
Start Over Descriptor "Tumor Necrosis Factor Ligand Superfamily Member 15 antagonists & inhibitors" Topic colitis
2 results on '"Tumor Necrosis Factor Ligand Superfamily Member 15 antagonists & inhibitors"'

1. TL1A blocking ameliorates intestinal fibrosis in the T cell transfer model of chronic colitis in mice.

Author

Li H, Song J, Niu G, Zhang H, Guo J, Shih DQ, Targan SR, and Zhang X

Subjects
Animals, Chronic Disease, Disease Models, Animal, Fibrosis metabolism, Homeostasis physiology, Male, Mice, Inbred C57BL, Tumor Necrosis Factor Ligand Superfamily Member 15 immunology, Tumor Necrosis Factor Ligand Superfamily Member 15 metabolism, CD4-Positive T-Lymphocytes metabolism, Colitis metabolism, Inflammation metabolism, Tumor Necrosis Factor Ligand Superfamily Member 15 antagonists & inhibitors
Abstract

Tumor necrosis factor like cytokine 1A (TL1A) is a member of the TNF superfamily. Accumulating evidence demonstrated the importance of TL1A in the pathogenesis of inflammatory bowel disease (IBD) and suggested a potential role of TL1A blocking in IBD therapy. Here we aimed to explore whether the anti-TL1A antibody could ameliorate intestinal inflammation and fibrosis in IBD. A T cell transfer model of chronic colitis was induced by intraperitoneal injection of CD4 + CD45RB high naive T cells isolated from either C57BL/6 wild type (WT) mice or LCK-CD2-Tl1a-GFP transgenic (L-Tg) mice into recombinase activating gene-1-deficient (RAG -/- ) mice. The colitis model mice were treated prophylactically or therapeutically with anti-Tl1a antibody or IgG isotype control. Haematoxylin and eosin staining (H&E staining), Masson's trichrome staining (MT staining) and sirius red staining were used to detect histopathological changes in colonic tissue; immunohistochemical staining was used to detect the expressions of collagen I, collagen III, TIMP1, vimentin, α-SMA and TGF-β1/Smad3. Results showed that anti-Tl1a antibody could reduce intestinal inflammation and fibrosis by inhibiting the activation of intestinal fibroblasts and reducing the collagen synthesis in the T cell transfer model of chronic colitis. The mechanism may be related to the inhibition of TGF-1/Smad3 signaling pathway., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Published
2018
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2. TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation.

Author

Takedatsu H, Michelsen KS, Wei B, Landers CJ, Thomas LS, Dhall D, Braun J, and Targan SR

Subjects
Adoptive Transfer, Animals, Anti-Inflammatory Agents pharmacology, Antibodies, Monoclonal pharmacology, Cells, Cultured, Chronic Disease, Colitis chemically induced, Colitis drug therapy, Colitis pathology, Colon drug effects, Colon pathology, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Dextran Sulfate, Disease Models, Animal, Female, GTP-Binding Protein alpha Subunit, Gi2 genetics, GTP-Binding Protein alpha Subunit, Gi2 metabolism, Gastrointestinal Agents pharmacology, Interferon-gamma metabolism, Interleukin-12 metabolism, Interleukin-17 metabolism, Intestinal Mucosa immunology, Lymphocyte Subsets drug effects, Lymphoid Tissue immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Interleukin antagonists & inhibitors, Receptors, Interleukin metabolism, Receptors, Tumor Necrosis Factor, Member 25 metabolism, Th1 Cells drug effects, Time Factors, Tumor Necrosis Factor Ligand Superfamily Member 15 antagonists & inhibitors, Up-Regulation, Colitis immunology, Colon immunology, Lymphocyte Activation drug effects, Lymphocyte Subsets immunology, Th1 Cells immunology, Tumor Necrosis Factor Ligand Superfamily Member 15 metabolism
Abstract

Background & Aims: TL1A is a tumor necrosis factor-like molecule that mediates a strong costimulation of T-helper (T(H)) 1 cells. Expression of TL1A is increased in the mucosa of Crohn's disease patients and murine models of ileitis. The aim of this study was to determine the possible role of TL1A in chronic intestinal inflammation., Methods: We used dextran sodium sulfate (DSS)-induced chronic colitis to investigate the effects of TL1A on the development of colitis. The cytokine profile in the gut-associated lymphoid tissue (GALT) was measured. Neutralizing anti-TL1A antibodies were injected intraperitoneally into DSS-induced chronic colitis and G protein alphai2(-/-) T-cell transfer colitis models. Severity of colitis was evaluated by body weight, colon length, histology, and cytokine production., Results: DSS-induced chronic colitis was characterized by the infiltration of CD4(+) T cells. TL1A, death receptor 3, interferon (IFN)-gamma, and interleukin (IL)-17 were increased significantly in GALT of DSS-treated mice. TL1A up-regulated both IFN-gamma production from T(H)1 cells and IL-17 production from T(H)17 cells in GALT CD4(+) T cells. Furthermore, IFN-gamma and IL-17 production from CD4(+) T cells, induced by IL-12 and IL-23 respectively, was enhanced synergistically by combination with TL1A. Anti-TL1A antibody prevented chronic colitis and attenuated established colitis by down-regulation of both T(H)1 and T(H)17 activation., Conclusions: Our results reveal that TL1A is an important modulator in the development of chronic mucosal inflammation by enhancing T(H)1 and T(H)17 effector functions. The central role of TL1A represents an attractive, novel therapeutic target for the treatment of Crohn's disease patients.

Published
2008
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