Inflammatory cytokine gene expression is a process strictly regulated by various mechanisms, including the negative regulation of signaling of cytokine receptors and of the activity of transcription factors such as STATs. These mechanisms involve endogenous proteins and is largely unknown, especially in periodontal diseases. Three groups of proteins, SHP, PIAS and SOCS modulate in a fairly specific manner JAK-STAT signaling and/or STAT activity. Periodontal diseases are infectious-inflammatory conditions of the supporting tissues of the teeth associated with increased levels of proinflammatory cytokines, but there are virtually no information regarding the role of these endogenous mediators of JAK-STAT during its course. The aims of this proposal include the study of the expression kinetics of inducible negative regulators, of their intracellular localization and of their physical interaction with their target proteins during the course of experimentally-induced periodontal disease. Using this model, we propose to evaluate the dynamics of expression, intracellular localization and physical interaction of SOCS-1, SOCS-3, PIAS1 and PIAS3 with STAT1 and STAT3 by means of real time RT-PCR, Western blotting and immunoprecipitation. Information derived from this proposal will contribute to the understanding of role of these endogenous negative regulators of JAK-STAT during inflammatory periodontal disease.
News published in Agência FAPESP Newsletter about the scholarship: