Finding
As the sustained TREM‐1 expression at the cell surface suffices to block the progress of a refractory state in human monocytes, our data indicate that TREM‐1 and MMPs orchestrate an “adaptive” form of innate immunity by modulating the human monocytes response to endotoxin.
Paper
Role of MMPs in orchestrating inflammatory response in human monocytes via a TREM‐1‐PI3K‐NF‐κB pathway
Citations: 29
Full textAbstract
The MMPs constitute a family of endopeptidases that can cleavage extracellular proteins. They are involved in a number of events; some of these include inflammatory processes. One of its targets is the TREM‐1, which has emerged as an important modulator of innate immune responses in mammals. This transmembrane glycoprotein possesses an Ig‐like ectodomain readily shed by MMPs to generate sTREM‐1. Whereas membrane‐anchored TREM‐1 amplifies inflammatory responses, sTREM‐1 exhibits anti‐inflammatory properties. Here we show that sustained cell surface expression of TREM‐1 in human monocytes, through metalloproteinase inhibition, counteracts the well‐characterized down‐regulation of several proinflammatory cytokines during the ET time‐frame, also known as M2 or alternative activation. In addition to the cytokines profile, other features of the ET phenotype were underdeveloped when TREM‐1 was stabilized at the cell surface. These events were mediated by the signal transducers PI3Ks and Syk. We also show that sTREM‐1 counteracts the proinflammatory response obtained by membrane TREM‐1 stabilization but failed to induce ET on naïve human monocytes. As the sustained TREM‐1 expression at the cell surface suffices to block the progress of a refractory state in human monocytes, our data indicate that TREM‐1 and MMPs orchestrate an “adaptive” form of innate immunity by modulating the human monocytes response to endotoxin.
Authors
V. Gómez-Piña, E. Martínez, I. Fernández-Ruíz
Journal
Journal of Leukocyte Biology