A Metalloproteinase Induces an Inflammatory Response in Preadipocytes with the Activation of COX Signalling Pathways and Participation of Endogenous Phospholipases A(2)

Author(s)

Janovits, Priscila Motta ^{[1, 2]} ; Leiguez, Elbio ^{[1, 2]} ; Portas, Viviane ^{[2, 3]} ; Teixeira, Catarina ^{[1, 2]}

Affiliation

^[1] Inst Butantan, Lab Farmacol, BR-05503900 Sao Paulo - Brazil

^[2] Inst Butantan, Ctr Excellence New Target Discovery CENTD, BR-05503900 Sao Paulo - Brazil

^[3] Inst Butantan, Lab Desenvolvimento & Inovacao, BR-05503900 Sao Paulo - Brazil

• Document type: Journal article
• Source: BIOMOLECULES; v. 11, n. 7 JUL 2021.
• Web of Science Citations: 0

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 BmooMP alpha-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 E-2 (PGE(2)) release. The results show that BmooMP alpha-I induced the release of PGE(2), prostaglandin I-2 (PGI(2)), monocyte chemoattractant protein-1 (MCP-1), and adiponectin by preadipocytes. BmooMP alpha-I-induced PGE(2) biosynthesis was dependent on group-IIA-secreted phospholipase A(2) (sPLA(2)-IIA), cytosolic phospholipase A(2)-alpha (cPLA-alpha), and cyclooxygenase (COX)-1 and -2 pathways. Moreover, BmooMP alpha-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 BmooMP alpha-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. (AU)

• FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support Opportunities: Research Grants - Applied Research Centers Program