title: Stimulatory Toll-like receptor 2 suppresses restraint stress-induced immune suppression.
abstract: Stress can enhance or suppress immune functions depending on a variety of factors. Our previous studies observed that Toll-like receptor 2 (TLR2) participates in chronic restraint stress-induced immune dysfunction. However, the mechanism by which TLR2 prevents immune suppression remains elusive. Our investigation found that stimulation of TLR2 by peptidoglycan (PGN) significantly attenuates splenocyte apoptosis and markedly blocks alterations of anti-apoptotic and apoptotic proteins. Activation of TLR2 inhibits chronic stress-reduced phosphorylation of c-Jun N-terminal kinase (JNK) and diminishes chronic stress-induced up-regulation of corticosterone production. Additionally, our data show that chronic stress causes a dramatic decrease of cytokine IL-2 level but an increase of IL-4 and IL-17 in CD4(+) T cells. Interestingly, PGN could block these alterations of cytokine levels. Collectively, our studies demonstrate that stimulation of TLR2 attenuates chronic stress-induced immune suppression by modulating apoptosis-related proteins and immunoregulatory agents.
authors.affiliation: Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37604, USA. dandanhu98@163.com
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: James
authors.initials: J
authors.lastname: Denney
authors.forename: Manfei
authors.initials: M
authors.lastname: Liang
authors.forename: Avani
authors.initials: A
authors.lastname: Javer
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yang
authors.forename: Ruiliang
authors.initials: R
authors.lastname: Zhu
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes; D004797:Enzyme-Linked Immunosorbent Assay; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010457:Peptidoglycan / Q000276:immunology / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012149:Restraint, Physical; D015398:Signal Transduction / Q000276:immunology*; D013315:Stress, Psychological / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism
chemical_list: D010457:Peptidoglycan; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
keywords: Apoptosis; Corticosterone; Immune response; JNK; PGN; Stress; TLR2; TUNEL; Toll like receptor 2; c-Jun N-terminal kinase; peptidoglycan; terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling