MicroRNA in TLR signaling and endotoxin tolerance

MA Nahid, M Satoh, EKL Chan - Cellular & molecular immunology, 2011 - nature.com
MA Nahid, M Satoh, EKL Chan
Cellular & molecular immunology, 2011nature.com
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 …
Abstract
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.
nature.com