Expression and function of macrophage‐inducible C‐type lectin (Mincle) in inflammation driven parturition in fetal membranes and myometrium. (13th March 2019)

• Record Type: Journal Article
• Authors: Lim, R.; Lappas, M.
• Is Part Of: Clinical and experimental immunology. Volume 197:Number 1(2019)
• Page Start: 95
• Page End: 110
• Publication Date: 2019-03-13
• Subjects: fetal membranes -- human labour -- inflammation -- Mincle -- myometrium; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13281
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: The pivotal role of inflammatory processes in human parturition is well known, but not completely understood. We have performed a study to examine the role of macrophage‐inducible C‐type lectin (Mincle) in inflammation‐associated parturition. Using human samples, we show that spontaneous labour is associated with up‐regulated Mincle expression in the myometrium and fetal membranes. Mincle expression was also increased in fetal membranes and myometrium in the presence of pro‐labour mediators, the proinflammatory cytokines interleukin (IL)‐1B and tumour necrosis factor (TNF), and Toll‐like receptor (TLR) ligands fsl‐1, poly(I:C), lipopolysaccharide (LPS) and flagellin. These clinical studies are supported by mouse studies, where an inflammatory challenge in a mouse model of preterm birth increased Mincle expression in the uterus. Importantly, elimination of Mincle decreased the effectiveness of proinflammatory cytokines and TLR ligands to induce the expression of pro‐labour mediators; namely, proinflammatory cytokines and chemokines, contraction‐associated proteins and prostaglandins, and extracellular matrix remodelling enzymes, matrix metalloproteinases. The data presented in this study suggest that Mincle is required when inflammatory activation precipitates parturition. Abstract : Summary sentence: The pattern recognition receptor macrophage‐inducible C‐type lectin (Mincle) is increased in fetal membranes and myometrium from labouring women and in the presence of proinflammatory and pro‐labour mediators, and in the uterus in a mouse model of inflammation‐induced preterm birth. In the absence of Mincle, the effectiveness of inflammatory insults to induce the expression and or secretion of pro‐labour mediators was reduced. These data suggest that Mincle is part of the process by which inflammation induces parturition.