Suppressive effects of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine on the Toll-like receptor signaling pathways

When various pathogens invade a host, toll-like receptors (TLRs) play a significant role in recognizing the pathogen-associated molecular patterns carried by the pathogens to induce innate immune reaction, followed by acquired immunity reaction. TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent pathways. To evaluate the therapeutic potential of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine (FPP), previously synthesized in our laboratory, its effect on signal transduction via the TLR signaling pathways was examined. FPP inhibited the activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) induced by TLR agonists, as well as inhibited the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. FPP also inhibited the activation of NF-κB and IRF3 when induced by the overexpression of downstream signaling components of the TLRs. As a result, FPP has potential to become a new therapeutic drug for many inflammatory diseases. •Inflammation is involved in numerous diseases.•Toll-like receptors (TLR) play a significant role in the induction of innate immune responses.•1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine is abbreviated to FPP.•FPP inhibited the NF-κB and IRF3 activation and COX-2, iNOS, and IP-10 expression induced by TLR agonists.•These results suggest that FPP can be developed as a potent anti-inflammatory drug.