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.
Highlights
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endoproteases responsible for the degradation of various proteins of the extracellular matrix (ECM)
We investigated the ability of BmooMPα-I, a P-I class metalloproteinase isolated from Bothrops moojeni snake venom, to activate the inflammatory response by preadipocytes in culture with a focus on (i) the release of prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2), cytokines, and adipokines; and (ii) the mechanisms involved in the release of PGE2 induced by this metalloproteinase
To investigate the action of BmooMPα-I in preadipocytes, we first assessed the ability of this metalloproteinase to induce the release of PGE2 in cultured preadipocytes by testing three concentrations of BmooMPα-I (0.06, 0.12, and 0.24 μM), which were added to the culture for 24 h
Summary
MMPs are a family of zinc-dependent endoproteases responsible for the degradation of various proteins of the extracellular matrix (ECM). In physiological conditions, when the expression and activity of MMPs are under strict control, these enzymes play important roles in tissue remodelling, host defense, angiogenesis, and immune response, as well as cell proliferation, migration, and differentiation [1,2,3,4]. When there is an imbalance between the levels of activated MMPs and their tissue inhibitors, these enzymes become important in the pathogenesis of several inflammatory diseases, such as arthritis, atherosclerosis, and obesity [1,3,5,6,7,8,9]. Increased circulating plasma levels of MMPs and increased expression of these enzymes, mainly of MMP-3, MMP-9, and MMP-13, have been reported in the inflamed tissues of patients suffering from inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, bowel disease, and neuroinflammation [1,3,8,10].
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