Evaluation of glutamine as modulator of the transcription factor NF-kB and c-Rel in macrophages and lymphocytes from IL-10 knock out mice subjected to dietary restriction

• Grant number: 15/02610-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 01, 2015
• End date: June 30, 2016
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Ricardo Ambrósio Fock
• Grantee: Dalila Cunha de Oliveira
• Supervisor: Bruce H. Horwitz
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Brigham and Women's Hospital (BWH), United States
• Associated to the scholarship: 14/14204-0 - Evaluation of glutamine as modulator of c-Rel and NFkB factors in macrophages and lymphocytes in a dietary restriction model, BP.DR

Abstract

Dietary restriction modify the innate and adaptive immune response, exerting effects on inflammatory and regulatory cytokine production also modifying the expression of genes directly involved in immune response. Macrophages and lymphocytes play key roles in innate and specific immune response and have high utilization rate of the amino acid glutamine, which is essential for energy and nitrogen supply. In addition, activation of macrophages and lymphocytes in vitro increases the transcription process and secretion of proteins, such as pro-inflammatory cytokines, allowing modulation of immune and inflammatory responses. This type of activation leads to an increased synthesis of messenger RNA, glutamine has an important role on this process, because this amino acid acts as a precursor of nitrogenous bases. In this context, it appears that the glutamine metabolism in macrophages and lymphocytes is essential for the cytokines synthesis and it is dependent on the extracellular concentration of glutamine. Cytokines, fall into two broad classes: pro-inflammatory and anti-inflammatory. In the classic immune response, the two antagonize one another in a carefully orchestrated manner in order to precisely regulate the vigor and duration of the immune response. Cytokines such as IL-10 develop regulatory roles controlling the production of pro inflammatory cytokines. It is produced by macrophages and lymphocytes, the deficiency of the IL-10 receptor can lead to a markedly proinflamatory cytokine production disrupting the inflammatory process. Thus, considering the modulatory effects of glutamine, and the effects exerted by dietary restriction on the immunity system, leading to higher synthesis of regulatory cytokines, we proposed in this project, addressing some complex aspects of immune regulation of the NF-kB family transcription factors, and the influence of glutamine supplementation modulating these processes in IL-10 knock-out mice subjected to dietary restriction. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CONAWAY, EVAN A.; DE OLIVEIRA, DALILA C.; MCINNIS, CHRISTINE M.; SNAPPER, SCOTT B.; HORWITZ, BRUCE H.. Inhibition of Inflammatory Gene Transcription by IL-10 Is Associated with Rapid Suppression of Lipopolysaccharide-Induced Enhancer Activation. JOURNAL OF IMMUNOLOGY, v. 198, n. 7, p. 2906-2915, APR 1 2017. (15/02610-6)

DE OLIVEIRA, DALILA CUNHA; HORWITZ, BRUCE HAROLD; FOCK, RICARDO AMBROSIO. Glutamine Modulates Cytokines Gene Expression in a Dose and Time Dependent Manner. FASEB JOURNAL, v. 31, p. 1-pg., 2017-04-01. (15/02610-6)