Growth factor and Th2 cytokine signaling pathways converge at STAT6 to promote arginase expression in progressive experimental visceral leishmaniasis.

ABSTRACT: Host arginase 1 (arg1) expression is a significant contributor to the pathogenesis of progressive visceral leishmaniasis (VL), a neglected tropical disease caused by the intracellular protozoan Leishmania donovani. Previously we found that parasite-induced arg1 expression in macrophages was dependent on STAT6 activation. Arg1 expression was amplified by, but did not require, IL-4, and required de novo synthesis of unknown protein(s). To further explore the mechanisms involved in arg1 regulation in VL, we screened a panel of kinase inhibitors and found that inhibitors of growth factor signaling reduced arg1 expression in splenic macrophages from hamsters with VL. Analysis of growth factors and their signaling pathways revealed that the Fibroblast Growth Factor Receptor 1 (FGFR-1) and Insuli

SUBMITTER: Osorio EY 

PROVIDER: S-EPMC4072777 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature