title: Essential role of IL-10/STAT3 in chronic stress-induced immune suppression.
abstract: Stress can either enhance or suppress immune functions depending on a variety of factors such as duration of stressful condition. Chronic stress has been demonstrated to exert a significant suppressive effect on immune function. However, the mechanisms responsible for this phenomenon remain to be elucidated. Here, male C57BL/6 mice were placed in a 50-ml conical centrifuge tube with multiple punctures to establish a chronic restraint stress model. Serum IL-10 levels, IL-10 production by the splenocytes, and activation of STAT3 in the mouse spleen were assessed. We demonstrate that IL-10/STAT3 axis was remarkably activated following chronic stress. Moreover, TLR4 and p38 MAPK play a pivotal role in the activation of IL-10/STAT3 signaling cascade. Interestingly, blocking antibody against IL-10 receptor and inhibition of STAT3 by STAT3 inhibitor S3I-201 attenuates stress-induced lymphocyte apoptosis. Inhibition of IL-10/STAT3 dramatically inhibits stress-induced reduction in IL-12 production. Furthermore, disequilibrium of Th1/Th2 cytokine balance caused by chronic stress was also rescued by blocking IL-10/STAT3 axis. These results yield insight into a new mechanism by which chronic stress regulates immune functions. IL-10/STAT3 pathway provides a novel relevant target for the manipulation of chronic stress-induced immune suppression.
authors: Dan
authors: D
authors: Hu
authors: Lei
authors: L
authors: Wan
authors: Michael
authors: M
authors: Chen
authors: Yi
authors: Y
authors: Caudle
authors: Gene
authors: G
authors: LeSage
authors: Qinchuan
authors: Q
authors: Li
authors: Deling
authors: D
authors: Yin
mesh_terms: D000818:Animals; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D012149:Restraint, Physical; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: C556062:IL10 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10