Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation

Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a key mediator of TNF receptor superfamily members and is important in both T helper (Th) cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5’s influence on inflammatory bowel diseases (IBDs), we invest...

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Main Authors: Jian Shang, Lixia Li, Xiaobing Wang, Huaqin Pan, Shi Liu, Ruohang He, Jin Li, Qiu Zhao
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/9453745
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author Jian Shang
Lixia Li
Xiaobing Wang
Huaqin Pan
Shi Liu
Ruohang He
Jin Li
Qiu Zhao
author_facet Jian Shang
Lixia Li
Xiaobing Wang
Huaqin Pan
Shi Liu
Ruohang He
Jin Li
Qiu Zhao
author_sort Jian Shang
collection DOAJ
description Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a key mediator of TNF receptor superfamily members and is important in both T helper (Th) cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5’s influence on inflammatory bowel diseases (IBDs), we investigated TRAF5 deficiency’s effect on dextran sulfate sodium- (DSS-) induced colitis. Colitis was induced in TRAF5 knockout (KO) mice and their wild-type (WT) littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4+ T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4+ T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.
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spelling doaj-art-32526731b67243788a36e9baa66cf0ff2025-02-03T00:59:07ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/94537459453745Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated InflammationJian Shang0Lixia Li1Xiaobing Wang2Huaqin Pan3Shi Liu4Ruohang He5Jin Li6Qiu Zhao7Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaTumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a key mediator of TNF receptor superfamily members and is important in both T helper (Th) cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5’s influence on inflammatory bowel diseases (IBDs), we investigated TRAF5 deficiency’s effect on dextran sulfate sodium- (DSS-) induced colitis. Colitis was induced in TRAF5 knockout (KO) mice and their wild-type (WT) littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4+ T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4+ T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.http://dx.doi.org/10.1155/2016/9453745
spellingShingle Jian Shang
Lixia Li
Xiaobing Wang
Huaqin Pan
Shi Liu
Ruohang He
Jin Li
Qiu Zhao
Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation
Mediators of Inflammation
title Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation
title_full Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation
title_fullStr Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation
title_full_unstemmed Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation
title_short Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation
title_sort disruption of tumor necrosis factor receptor associated factor 5 exacerbates murine experimental colitis via regulating t helper cell mediated inflammation
url http://dx.doi.org/10.1155/2016/9453745
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