Down-regulation of mitogen-activated protein kinases and nuclear factor-B signaling is involved in rapamycin suppression of TLR2-induced inflammatory response in monocytic THP-1 cells

作者：Sun, Ruili; Zhang, Yi; Ma, Shijiang; Qi, Hengtian; Wang, Mingyong; Duan, Juhong; Ma, Shujun; Zhu, Xiaofei; Li, Guancheng; Wang, Hui^*

来源：Microbiology and Immunology, 2015, 59(10): 614-622.

DOI：10.1111/1348-0421.12321

• MAPKs
• nuclear factor-B
• rapamycin
• Toll-like receptor 2

Tripalmitoyl-S-glycero-Cys-(Lys) 4 (Pam3CSK4) interacted with TLR2 induces inflammatory responses through the mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-B) signal pathway. Rapamycin can suppress TLR-induced inflammatory responses; however, the detailed molecular mechanism is not fully understood. Here, the mechanism by which rapamycin suppresses TLR2-induced inflammatory responses was investigated. It was found that Pam3CSK4-induced pro-inflammatory cytokines were significantly down-regulated at both the mRNA and protein levels in THP-1 cells pre-treated with various concentrations of rapamycin. Inhibition of phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT) signaling did not suppress the expression of pro-inflammatory cytokines, indicating that the immunosuppression mediated by rapamycin in THP1 cells is independent of the PI3K/AKT pathway. RT-PCR showed that Erk and NF-B signal pathways are related to the production of pro-inflammatory cytokines. Inhibition of Erk or NF-B signaling significantly down-regulated production of pro-inflammatory cytokines. Additionally, western blot showed that pre-treatment of THP-1 cells with rapamycin down-regulates MAPKs and NF-B signaling induced by Pam3CSK4 stimulation, suggesting that rapamycin suppresses Pam3CSK4-induced pro-inflammatory cytokines via inhibition of TLR2 signaling. It was concluded that rapamycin suppresses TLR2-induced inflammatory responses by down-regulation of Erk and NF-B signaling.

• 出版日期2015-10
• 单位新乡医学院; 中南大学