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Effect of protein rLopap and peptide derived on human chondrocytes in the inflammatory model with interleucin-1B (IL-1b)

Grant number: 18/04467-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2018
Effective date (End): December 31, 2018
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Ana Marisa Chudzinski-Tavassi
Grantee:Gabriela Simões Pazelli
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The human contact with the taturanas of the genus Lonomia obliqua causes accidents involving hemorrhagic syndrome; studies using the crude extract of their bristles proved that there is induction of clot formation. One of the pro-coagulant proteins responsible for action was identified, Lopap, a direct agent in endothelial cells and tissue remodeling. In vivo studies in mice, after contact with the crude extract, showed an inflammatory response; the inflammation signaling pathways interact with the coagulation cascade by means of molecules that lead to inflammatory responses characterized by leukocyte migration and chemotaxis, as well as adhesion to the endothelium. Therefore, studies on the mechanisms of signaling and action of this protein and derived peptides becomes interesting for the treatment of diseases involving inflammatory processes such as osteoarthritis (OA). OA is a degenerative disease of the joints, characterized by the degradation of the extracellular matrix (ECM) and chondrocytes, present in the cartilage, causing pain in the patients. In these patients, there is an increase in mediators in synovial fluid, such as interleukins (mainly IL-1B) and nitric oxide, which induce chondrocyte apoptosis. Hyaluronic acid is a natural component of ECM and reduces the effects caused by IL-1B, so it is widely used in the treatment of OA. However, further studies on new molecular targets are still needed to treat the disease. With this, the present project aims to evaluate the anti-inflammatory and cytoprotective effect of Lopap and its potential use in the treatment for Osteoarthritis. (AU)