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Impact of epididymitis induced by lipopolysaccharide from E. coli and lipotheicoic acid from S. aureus on the expression of genes involved in TLR4- and TLR2/TLR6-signaling pathways in the mouse epididymis

Grant number: 17/25982-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2018
Effective date (End): December 31, 2018
Field of knowledge:Biological Sciences - Pharmacology
Principal researcher:Erick José Ramo da Silva
Grantee:Priscila Gasperini Camolesi de Almeida
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated research grant:15/08227-0 - A study on EPPIN as a drug target for male contraception: developing a new animal model to test the efficacy of male contraceptive drugs, AP.JP

Abstract

The epididymis is an organ of the male reproductive tract that plays crucial roles on sperm maturation. Epididymitis, inflammation of the epididymis, is a highly prevalent urogenital disease in the investigation of male infertility factors. Bacterial infections that reach the epididymis via retrograde urethral ascension are the most common etiology of epididymitis. As part of its innate immune system, the epididymis expresses members of the Toll-like receptor (TLR) family, including TLR4 and TLR2/TLR6, which are activated by lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteichoic acid (LTA) from Gram-positive bacteria, respectively. We recently demonstrated that epididymitis induced by LPS or LTA resulted in the recruitment of distinct respective sets of inflammatory mediators in the epididymis. In order to further investigate how the epididymis triggers inflammatory responses upon infection, we proposed herein to evaluate the effects of LPS- and LTA-induced acute epididymitis on the expression profile of genes involved in TLR4 and TLR2/TLR6 signaling cascade. We will explore the experimental model of acute epididymitis induced by the injection of ultrapure LPS from E. coli or LTA from S. aureus into the lumen of the vas deferens of mice, pre-treated or not with the inhibitor of NFKB activation PDTC, to investigate the effects of these bacterial-derived products on the mRNA expression of Tlr4, Tlr2, Tlr6, Myd88, Trif, Cd14 and Cd36, as well as on the cellular distribution of TLR4 e TLR2 in the epididymis. This project will open new roads to the investigation of TLR signaling cascade in the epididymis and their relevance to the physiopathology of epididymitis. (AU)

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