SOCS-1 Protects against Chlamydia pneumoniae-Induced Lethal Inflammation but Hampers Effective Bacterial Clearance1
SOCS-1 Protects against Chlamydia pneumoniae-Induced Lethal Inflammation but Hampers Effective Bacterial Clearance1
复制标题
SOCS-1 可预防肺炎衣原体引起的致命炎症，但会阻碍有效的细菌清除1
作者：
Tang;Patrik Stark;K. Janik;H. Wigzell;M. Rottenberg
细胞因子信号转导抑制因子1（SOCS 1）在抑制STAT 1介导的反应中起主要作用。STAT 1依赖性应答对于抵抗肺炎衣原体感染至关重要。我们研究了SOCS 1和SOCS 3的表达调控，以及SOCS 1在感染C.小鼠肺炎。体外培养的骨髓源性巨噬细胞（BMM）和树突状细胞以及体内培养的肺组织均显示C.肺炎。SOCS 1 mRNA水平的增加依赖于IFN-αβ，但不依赖于IFN-γ。SOCS 1 mRNA在体内的积累不需要T或B细胞。在SOCS 1 −/− BMM中，抑制诱导的STAT 1磷酸化发生得更快。与此一致，在C.肺炎感染的SOCS 1-/-BMM。令人惊讶的是，C。SOCS 1减弱了BMM中肺炎杆菌感染诱导的IFN-α、IFN-β和IFN-γ表达。C. RAG 1 −/−/SOCS 1 −/−小鼠的肺炎感染诱导了快速致死性炎症，伴随着肺细菌负荷减少和iNOS和IDO水平升高，但IL-1β、IL-6或TNF-α mRNA水平不变。综上所述，C.肺炎链球菌感染诱导STAT 1、IFN-αβ依赖性和IFN-γ非依赖性SOCS 1 mRNA积累。SOCS 1的存在控制了感染诱导的致死性炎性疾病，但削弱了细菌控制。
Suppressor of cytokine signaling 1 (SOCS1) plays a major role in the inhibition of STAT1-mediated responses. STAT1-dependent responses are critical for resistance against infection with Chlamydia pneumoniae. We studied the regulation of expression of SOCS1 and SOCS3, and the role of SOCS1 during infection with C. pneumoniae in mice. Bone marrow-derived macrophages (BMM) and dendritic cells in vitro or lungs in vivo all showed enhanced STAT1-dependent SOCS1 mRNA accumulation after infection with C. pneumoniae. Infection-increased SOCS1 mRNA levels were dependent on IFN-αβ but not on IFN-γ. T or B cells were not required for SOCS1 mRNA accumulation in vivo. Infection-induced STAT1-phosphorylation occurred more rapidly in SOCS1−/− BMM. In agreement, expression of IFN-γ responsive genes, but not IL-1β, IL-6, or TNF-α were relatively increased in C. pneumoniae-infected SOCS1−/− BMM. Surprisingly, C. pneumoniae infection-induced IFN-α, IFN-β, and IFN-γ expression in BMM were attenuated by SOCS1. C. pneumoniae infection of RAG1−/−/SOCS1−/− mice induced a rapid lethal inflammation, accompanied by diminished pulmonary bacterial load and increased levels of iNOS and IDO but not IL-1β, IL-6, or TNF-α mRNA. In summary, C. pneumoniae infection induces a STAT1, IFN-αβ-dependent and IFN-γ independent SOCS1 mRNA accumulation. Presence of SOCS1 controls the infection-induced lethal inflammatory disease but impairs the bacterial control.
影响因子：
11.8
作者：
EKMAN, MR;GRAYSTON, JT;SAIKKU, P
通讯作者：
SAIKKU, P
影响因子：
56.9
作者：
HUANG, S;HENDRIKS, W;AGUET, M
通讯作者：
AGUET, M
DOI：
10.1016/j.bbrc.2004.12.074
发表时间：
2005-02-18
影响因子：
3.1
作者：
Ramana, CV;Kumar, A;Enelow, R
通讯作者：
Enelow, R