A Metalloproteinase Induces an Inflammatory Response in Preadipocytes with the Activation of COX Signalling Pathways and Participation of Endogenous Phospholipases A2

Abstract

Matrix metalloproteinases (MMPs) are proteolytic enzymes that have been associated with the pathogenesis of inflammatory diseases and obesity. Adipose tissue in turn is an active endocrine organ capable of secreting a range of proinflammatory mediators with autocrine and paracrine properties, which contribute to the inflammation of adipose tissue and adjacent tissues. However, the potential inflammatory effects of MMPs in adipose tissue cells are still unknown. This study investigates the effects of BmooMPα-I, a single-domain snake venom metalloproteinase (SVMP), in activating an inflammatory response by 3T3-L1 preadipocytes in culture, focusing on prostaglandins (PGs), cytokines, and adipocytokines biosynthesis and mechanisms involved in prostaglandin E2 (PGE2) release. The results show that BmooMPα-I induced the release of PGE2, prostaglandin I2 (PGI2), monocyte chemoattractant protein-1 (MCP-1), and adiponectin by preadipocytes. BmooMPα-I-induced PGE2 biosynthesis was dependent on group-IIA-secreted phospholipase A2 (sPLA2-IIA), cytosolic phospholipase A2-α (cPLA2-α), and cyclooxygenase (COX)-1 and -2 pathways. Moreover, BmooMPα-I upregulated COX-2 protein expression but not microsomal prostaglandin E synthase-1 (mPGES-1) expression. In addition, we demonstrate that the enzymatic activity of BmooMPα-I is essential for the activation of prostanoid synthesis pathways in preadipocytes. These data highlight preadipocytes as important targets for metalloproteinases and provide new insights into the contribution of these enzymes to the inflammation of adipose tissue and tissues adjacent to it.

Mapping the Immune Cell Microenvironment with Spatial Profiling in Muscle Tissue Injected with the Venom of Daboia russelii

“…The processes of skin re-epithelization and skeletal muscle repair and regeneration following acute venom-induced tissue damage have also been investigated [ 16 , 17 , 18 ]. In turn, other studies have assessed the activation induced by venoms and toxins on a variety of cell types in vitro, such as macrophages [ 19 , 20 , 21 ], mast cells [ 22 ], fibroblasts [ 23 ], adipocytes [ 24 ], and synoviocytes [ 25 ]. This large body of information has led to the understanding that a complex interplay between cells and mediators is involved in tissue damage, inflammation, repair, and regeneration as a consequence of the actions of venoms and toxins.…”