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Mohammed Shukur

Mohammed Shukur

University of Nottingham, United Kingdom

Title: Immune responses to Mycobacterium avium infection and the role of MAPK pathway in regulation of signal transduction during the infection

Biography

Biography: Mohammed Shukur

Abstract

Mycobacterial infection is a major problem in both human and animal health. Several cell signaling pathways are involved in the mediation of expression of a number of cytokines induced by mycobacterial infection. The mitogen activated protein kinase (MAPK) pathway plays a crucial role in the pathogenesis of mycobacterial infection. In this study we aimed to evaluate the role of ERK and p38 MAPK in cellular regulation by Mycobacterium avium infection in human and chicken macrophages-like cells. THP-1 and HD11 cells were infected with eight clinical isolates of Mycobacterium avium. The cells were pre-treated with highly specific inhibiters of the ERK (PD98059 or U0126) and p38 (SB203580) pathways 30 min prior to infection and the levels of cytokine production at 6 and 24 hour post infection were assessed using ELISA and RT-qPCR. M. avium infection resulted in differential expression of cytokines and chemokines in THP-1 and HD11 cells. Treatment of the cells with PD98059 or U0126 inhibited production of cytokines in THP-1 and completely blocked their expression in HD11 cells. In addition, p38 inhibition differentially modulated cytokine production in THP-1 cells compared to non-inhibited M. avium-infected cells. It inhibited release of IL-6 while the level of IL-1β and TNF-α showed an increase in THP-1 cells in response to M. avium infection following treatment of the cells with SB203580. The results suggest that signalling events are significantly different in avian and human cells following M. avium infection. Both p38 and ERK are involved in regulation of IL-6 production while p38 negatively regulates IL-1β and TNF-α production in response to M. avium in THP-1 cells. In HD11 cells, it is suggested that multiple signal pathways simultaneously participate in regulation of cytokine signal transduction during M. avium infection.

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