Triptolide inhibits inducible nitric oxide synthase expression induced by toll-like receptor agonists

Abstract

Toll-like receptors (TLRs) play an important role in the induction of innate immune responses recognizing many pathogen-associated molecular patterns. The activation of TLRs triggers two downstream signaling pathways; MyD88- (myeloid differential factor 88) and TRIF-(toll-interleukin-1 receptor domain-containing adapter inducing interferon-β) dependent pathways leading to the induction of pro-inflammatory gene products such as inducible nitric oxide synthase (iNOS). The present study investigated the effect of triptolide (TP), a natural component of Tripterygium wilfordii Hook. F, on inflammation by modulating iNOS expression induced by TLR agonists in murine macrophages. TP suppressed iNOS expression induced by lipopolysaccharide (TLR4 agonist), polyriboinosinic polyribocytidylic acid (TLR3 agonist), and macrophage-activating lipopeptide 2-kDa (TLR2 and TLR6 agonist). All the results suggest that TP can modulate TLR signaling pathways and subsequent chronic inflammatory responses.