Role of IL6 in the modulation of the transcriptional factor NF-kB in pancreatic beta cells

• Grant number: 17/16513-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2018
• Effective date (End): December 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Fernanda Ortis
• Grantee: Viviane Rosa de Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

During the development of Type 1 Diabetes (T1D) pancreatic islets are invaded by immune cells which directly or via secretion of pro-inflammatory cytokines lead to pancreatic ² cells dysfunction and dead. In vitro exposure of ² cells to pro-inflammatory cytokines, such as IL-1², TNF and IFN-³ lead to dysfunction and apoptosis. The transcription factor NF-ºB has an important role in these deleterious effects, manly via induction of the inducible oxide synthase. Physical exercise, in combination with diet and exogenous insulin, has therapeutic used for glycemic control in DM1, since it improves insulin-independent glucose capitation. Recent studies indicate that secretion of interleukin (IL) 6 from skeletal muscle during physical exercise can prevent cytokine induced ² cell death, as well improve its function in DM1 animal models. These beneficial effects on ² cells are not very well understood, but it could be related to NF-ºB modulation, since leads to reduction of cytokine induced iNOS expression. Thus, our aim is to study the effects of IL-6 on the cytokine-induced pro-apoptotic activation of NF-ºB in pancreatic ² cells. The better understanding of these mechanisms involved in the prevention of ² cell demise could be used in the development of a therapy to prevent ² cell destruction. (AU)