Transforming Growth Factor-Beta Promotes Rhinovirus Replication in Bronchial Epithelial Cells by Suppressing the Innate Immune Response

被引：68

作者：

Bedke, Nicole ^{[1
]}

Sammut, David ^{[1
]}

Green, Ben ^{[1
]}

Kehagia, Valia ^{[1
]}

Dennison, Patrick ^{[1
,2
]}

Jenkins, Gisli ^{[3
]}

Tatler, Amanda ^{[3
]}

Howarth, Peter H. ^{[1
,2
]}

Holgate, Stephen T. ^{[1
,2
]}

Davies, Donna E. ^{[1
,2
]}

机构：

[1] Univ Southampton, Fac Med, Southampton Univ Hosp, Acad Unit Clin & Expt Sci, Southampton SO9 5NH, Hants, England

[2] Southampton Univ Hosp, Natl Inst Hlth Res, Resp Biomed Res Unit, Southampton, Hants, England

[3] Univ Nottingham, City Hosp Nottingham, Nottingham NG7 2RD, England

来源：

PLOS ONE | 2012年 / 7卷 / 09期

基金：

英国医学研究理事会;

关键词：

IN-VITRO; ASTHMA; EXPRESSION; ACTIVATION; MECHANISMS; INFECTION; PROTEINS; AIRWAYS; EXACERBATIONS; INFLAMMATION;

D O I：

10.1371/journal.pone.0044580

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-beta, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-beta(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-beta antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-beta(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-beta on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-beta and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-beta contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.

引用

页数：13

共 38 条

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