The LTB4/MyD88 axis in sterile inflammation and sepsis in experimental models of diabetes.

Author(s)

Luciano Filgueiras Ribeiro Junior

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2014-08-18

Examining board members

Sonia Jancar Negro; Niels Olsen Saraiva Câmara; Heraldo Possolo de Souza; Iolanda de Fátima Lopes Calvo Tibério; Lício Augusto Velloso

• Advisor: Sonia Jancar Negro; Joilson de Oliveira Martins

Abstract

Type 1 diabetes (T1D) is associated with sterile inflammation (SI) and increased sepsis susceptibility. Sepsis induces Systemic Inflammatory Response Syndrome (SIRS) and Acute Lung Injury (ALI). Leukotriene (LT) B4 is produced in inflammatory conditions and induces MyD88 expression in macrophages (MA). We hypothesized that T1D induce LB4 that promotes SI contributing to SIRS, sepsis susceptibility and ALI. Diabetics presented higher levels of LTB4 and e IL-1b in the serum and MA expressed more MyD88/STAT-1. STAT-1 expression was induced by c-Jun on LTB4 dependent manner. Insulin treatment restored LTB4 and STAT-1/MyD88 levels and inhibition of LTB4 restored MyD88 and IL-1b levels. During sepsis, 5LO inhibition increased diabetics survival and inhibited SIRS- lower levels of IL-1b and IL-10 in the serum and TNF-a and IL-1b in the peritoneal cavity. Lungs from diabetics presented milder ALI that correlated with high levels of SOCS-1, low levels of MyD88 and impaired NFkB activation in alveolar macrophages. (AU)

• FAPESP's process: 10/09388-3 - Molecular and cellular aspects of the lung inflammation caused by sepsis in diabetic and non diabetic rats
• Grantee: Luciano Filgueiras Ribeiro Junior
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)