Characterization of a luciferase expression assay induced by aryl hydrocarbon receptor activation

• Grant number: 14/16630-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2014
• Effective date (End): December 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Rafael Paulino Rimoldi
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

The aryl hydrocarbon receptor (AhR) is a transcription factor activated by ligands that is related to toxic response and elimination of xenobiotics. After its activation, the AhR transmigrates to cell nucleus, inducing the expression of several genes. Amont these genes there are xenobiotic metabolizing enzymes such as cytochromes P450 - CYP1A1, CYP1A2 and CYP1B1 and cytokines such as IL-8 and IL-22. Recently, AhR has been associated with the modulation of adaptive autoimmune response, playing an important role in the differentiation of T helper cells Th17, which are pathogenic. Our research group has identified an important role of AhR in development of human rheumatoid arthritis and murine experimental arthritis by modulating the generation of Th17 cells. Still, we found that the AhR plays a central role in smoking-induced arthritis aggravation observed in patients with rheumatoid arthritis. One of the goals of the CRID is the development of new molecular entities capable of blocking the activation of AhR for therapeutic use in autoimmune diseases. To do this, we need a biological assay for functional characterization of these molecules. The aim of this project is to develop and characterize a rapid bioassay to be used in the identification of new compounds with agonist and antagonist activity of AhR.