Evaluation of the transcription factor NFκB signaling pathway activated by TNF-α in a protein malnutrition model

Author(s)

Dalila Cunha de Oliveira

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2013-10-17

Examining board members

Ricardo Ambrosio Fock; Luciana Cristina Mirotti; Hosana Gomes Rodrigues

• Advisor: Ricardo Ambrosio Fock

Abstract

Malnutrition is a nutritional condition that consists in a major public health issue and affects a considerable part of the global population. Currently, It is known that many aspects of the immunological response can be altered due to the malnutrition impairment, among them functional changes, for instance, cell migration reduction, phagocytosis, bactericidal response, as well as changes in the reactive oxygen and nitrogen species production, besides, substantially cell receptors expression impaired, responsible for the recognition of pathogens and changes in the production of proinflammatory cytokines, such as TNF-α. This cytokine is primarily produced by macrophages, and it is associated to a wide range of biological activities, including the inflammation processes, growing, differentiation, and apoptosis. The TNF-α act through the linkage to distinct receptors, TNFR-I and TNFR-II. The TNFR-I receptor activation, however, is responsible for most TNF-α effects, and triggers a series of intracellular events that mainly result in the activation of the NFκB transcription factor. Regarding the relevance of this signaling pathway mediated by the TNF-α, we evaluated through a protein malnutrition model the signaling pathway for the NFκB transcription factor mediated by the TNF-α through TNFR-I. Adult male Balb/c mice, were submitted to a protein malnutrition and after a loss of nearly 20% body weight, peritoneal macrophages were collected and cultivated, or not with TNF-α. The supernatant was collected for cytokine production evaluation (IL-1α, IL-1β, IL-6, IL-12, and IL-10) and the cell for TNFR-I expression evaluation, as well as the proteins of the signaling pathway (TRADD, TRAF, RIP, IKK, IKBα, p IKBα, NFκB, and p NFκB). The compiled results highlights that the malnourished animals present signs of anemia, leukopenia, and decrease of bone marrow cellularity and peritoneal cavity. The results presented reduction of the TNFR-I expression, in addition to the phosphorylated portions of the IKBα and the NFκB expression, associated to a decrease in the production of IL-1β and IL-12. In this essay we perceive the aspects related to the innate immune response, and the outcome data allowed us to conclude that the nutritional status interferes on the macrophages activation and the response capabilities of these cells. (AU)

• FAPESP's process: 11/14247-2 - Signaling pathways evaluation of the transcription factor NFkB activated by TNF-a in a model of protein deficiency
• Grantee: Dalila Cunha de Oliveira
• Support Opportunities: Scholarships in Brazil - Master