Role of MMPs in orchestrating inflammatory response in human monocytes via a TREM-1-PI3K-NF-κB pathway

• DOI: 10.1189/jlb.0711340
• Publication Date: 2012-03-30T04:52:53Z
• Authors: Vanesa Gómez-Piña; Eriel Martínez; Irene Fernández-Ruíz; Carlos del Fresno; Alessandra Soares...; Teresa Jurado; María Siliceo; Victor Toledano; Rosa Fernández-Pa...; Francisco García-Rio; Francisco Arnalich; Subhra K Biswas; Eduardo López-Col...
• Keywords: Proinflammatory cytokine; Ectodomain; Monocyte

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