摘要
Toll-like receptors(TLRs)in innate immune cells are the prime cellular sensors for microbial components.TLR activation leads to the production of proinflammatory mediators and thus TLR signaling must be properly regulated by various mechanisms to maintain homeostasis.TLR4-ligand lipopolysaccharide(LPS)-induced tolerance or cross-tolerance is one such mechanism,and it plays an important role in innate immunity.Tolerance is established and sustained by the activity of the microRNA miR-146a,which is known to target key elements of the myeloid differentiation factor 88(MyD88)signaling pathway,including IL-1 receptor-associated kinase(IRAK1),IRAK2 and tumor-necrosis factor(TNF)receptor-associated factor 6(TRAF6).In this review,we comprehensively examine the TLR signaling involved in innate immunity,with special focus on LPS-induced tolerance.The function of TLR ligand-induced microRNAs,including miR-146a,miR-155 and miR-132,in regulating inflammatory mediators,and their impact on the immune system and human diseases,are discussed.Modulation of these microRNAs may affect TLR pathway activation and help to develop therapeutics against inflammatory diseases.
基金
supported in part by a grant from the Lupus Research Institute,Andrew J.Semesco Foundation,and National Institutes of Health(grant AI47859)
supported by NIAMS Rheumatology training grant T32 AR007603.
