The role of CD14 receptor on the metabolic regulation of macrophages stimulated with the venom from Tityus serrulatus scorpion

Author(s)

Luana Henrique de Macedo

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2020-08-10

Examining board members

Lucia Helena Faccioli; Anderson de Sá Nunes; Manuela Berto Pucca

• Advisor: Lucia Helena Faccioli

Abstract

The venom of Tituys serrulatus scorpion (TsV) is constituted by several compounds, which interact with innate immune cells and trigger signaling cascades that culminate on the inflammatory process. In humans, TsV envenomings induce alterations in several organs, deregulate ionic channels and can be fatal. Recent studies from our group described that macrophages are one of the main innate immune cells to recognize TsV. This process is performed by pattern recognition receptors (PRRs), in which the CD14 receptor is presented in macrophage surfaces, which when activated, results in the production of pro-inflammatory mediators. Recent observations implicate CD14 on a general metabolic regulation, since CD14-deficient animals do not become obese and they do not develop insulin resistance or cardiac complications associated to obesity. However, the molecular mechanisms by which CD14 coordinates the metabolic activity of immune system cells have not been elucidated. In this project, we investigate the role of CD14 on the metabolism of bone marrow derived macrophages (BMDMs) and peritoneal macrophages (MPs) of C57BL/6 and CD14-/- after the stimulation with TsV or LPS. We evaluated metabolic alterations resulting from the two stimuli, which were also compared between different bone marrow derived macrophages or residents in the peritoneal cavity. For this purpose, we used high resolution mass spectrometry coupled with liquid chromatography, a state- of-art technology on the field of metabolomics and systems biology. The data were analyzed using computational biology programs specifically designed for statistical analysis and functional analysis. The data were analyzed using computational biology programs specifically designed for statistical analysis and functional analysis. Our results demonstrated that the CD14 molecule contributes to the disturbance of different metabolic pathways between BMDMs and MPs, which are different according to the stimulus received, but include metabolism of amino acids, fatty acids, vitamins and urea cycle. This project has great potential for the design of new therapeutic strategies in TsV poisoning and related diseases/conditions. (AU)

• FAPESP's process: 18/10929-0 - The role of CD14 receptor on the metabolic regulation of macrophages stimulated with the venom from Tityus serrulatus scorpion
• Grantee: Luana Henrique de Macedo
• Support Opportunities: Scholarships in Brazil - Master