The role of nuclear factor kappa B (NF-kB) and the IL-12/23-IFN-g axis in the activation of the NADPH oxidase system.

Author(s)

Walmir Cutrim Aragão Filho

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2009-03-26

Examining board members

Antonio Condino Neto; Marcelo Nicolas Muscara; Pérsio Roxo Júnior

• Advisor: Antonio Condino Neto

Abstract

The NADPH oxidase system is an enzymatic complex that generates superoxide. The NF-kB is a transcriptional factor involved in the expression of several genes related to the inflammatory response. The IL-12/23-IFN-g axis defects lead to recurrent infections and to the mendelian susceptibility of mycobacterial disease (MSMD), and they can decrease the gp91-phox expression (a NADPH oxidase component). We studied the NF-kB and the IL-12/23-IFN-g axis defects consequences on the regulation of CYBA, NCF1, NCF2 and NCF4 genes of the human NADPH oxidase system in U937 cells, and in B EBV cells from patients with EDA-ID, DGC, or patients with IL-12/23-IFN-g axis defects. The NCF1 and NCF2 gene expression was decreased in IL-12/23-IFN-g axis defects cells (IFNGR1 and INFGR2) and in U937 IkB S32A/S36A cells. NCF1 gene expression was decreased in EDA-ID S32I and in EDA-ID NEMO/IKKg W420X cell lineages. The NF-kB and the IFNGR1 and INFGR2 are necessary for NCF1 and NCF2 gene expression and activation of the human NADPH oxidase in this model system. (AU)