Signaling pathways involved in the regulation of COX2 expression mediated by kinin B1 and B2 receptors agonists

• Grant number: 11/20475-8
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: January 01, 2012
• End date: February 29, 2012
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Pedro Paulo Chaves de Souza
• Grantee: Jonas Bianchi
• Supervisor: Vincent Everts
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Academic Centre for Dentistry Amsterdam (ACTA), Netherlands
• Associated to the scholarship: 11/06668-8 - Effect of kinins and P. gingivalis LPS on the expression of COX2 and cytokines in mice gingiva., BP.IC

Abstract

Bradykinin is a nonapeptide involved in inflammation, triggering to the inflammatory signs and symptoms when injected in animal tissues. It acts through the B2 receptor that is constitutively expressed in most tissues, and after activation this receptor is desensitized. The metabolite DABK acts through another receptor, the B1 receptor, that shares 36% identity with the B2 receptor, but is almost absent in normal conditions. The investigation of the kallikrein-kinin system in bone metabolism has been performed in vitro, and it has been shown that these peptides are capable of inducing osteoclastogenesis and bone resorption, and this effect is dependent on COX2 production. The participation of kinins in bone resorption leaded us to investigate the participation of these peptides in periodontal disease. Thus, we used gingival fibroblasts and shown that COX2 is up-regulated by BK and DABK in a dose-dependent and time-dependent manner in these cells. Therefore, the next step is to determine which signaling pathways are involved. For this porpoise, we will perform western blot experiments for the activation of different kinases, such as p38 MAPK, ERK MAPK, JNK MAPK, AKT MAPK and IºB-±, and also use inhibitors for these pathways to analyze their participation on COX-2 up regulation by kinins. (AU)