Evaluation of the molecular mechanisms involved in the iNOS expression by NAIP5/NLRC4-Caspase-1 axis.

Author(s)

Carina Buzzo de Lima

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2014-02-07

Examining board members

Karina Ramalho Bortoluci; Maria Regina D'Imperio Lima; Joel Machado Junior; Sergio Costa Oliveira; Alessandra Pontillo

• Advisor: Karina Ramalho Bortoluci

Abstract

Recognition of flagellin is shared by transmembranic TLR5 and cytosolic NAIP5/NLRC4. However, little is known about the individual effector mechanisms induced by extra and intracellular flagellin. Here, we have demonstrated that cytosolic flagellin-stimulated macrophages (FLA-BSDot) induced iNOS expression, an enzyme responsible for the production of nitric oxide (NO). iNOS expression was dependent of the NAIP5/NLRC4/caspase-1 axis and independent of IL-1β, IL-18 and MyD88, discarding TLRs signaling pathway. Still, this pathway do not require the activation of IRF-1 transcriptional factor, but involves NF-kB activation as well as the cleavage of the enzyme, PARP-1 (poly(ADP-ribose)polymerase-1). Finally, we have evaluated the biological relevance of this pathway in the control of the infections by L. pneumophila e S. Typhimurium, which define an additional effector mechanism to the control of pathogens. (AU)

• FAPESP's process: 09/16966-6 - Molecular Pathways involved in cytosolic flagellin-induced iNOS expression: Consequences for macrophage resistance against infections.
• Grantee: Carina Buzzo de Lima
• Support Opportunities: Scholarships in Brazil - Doctorate