Pam3CSK4, interacted with TLR2, induces the inflammatory response through MAPKs and NF-κB signal pathway, and Rapamycin can suppress TLR-induced inflammatory response, but the detailed molecular mechanism is not fully understood. Here we investgated the mechanism by which Rapamycin suppressed TLR2-induced inflammatory response. The results showed 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. The inhibition of PI3K/AKT signaling did not down-regulate the levels of pro-inflammatory cytokines, indicating that the immunosuppression mediated by Rapamycin in THP1 cells was independent on the PI3K/AKT pathway. RT-PCR results showed that Erk and NF-κB signal pathways were related to the production of pro-inflammatory cytokines. Inhibition of Erk or NF-κB signaling significantly down-regulated the production of the pro-inflammatory cytokines. Meanwhile, Western blot results showed that the pre-treatment of THP-1 cells with Rapamycin down-regulated MAPKs and NF-κB signaling induced by Pam3CSK4 stimulation, suggesting that Rapamycin suppressed Pam3CSK4-induced pro-inflammatory cytokines via inhibition of TLR2 signaling. So we draw a conclusion that Rapamycin suppressed TLR2-induced inflammatory response by down-regulation of Erk and NF-κB signaling.

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