Open AccessActivation of p38 Mitogen-Activated Protein Kinase AttenuatesLeishmania donovaniInfection in Macrophages
Author(s) -
M Junghae,
John G. Raynes
Publication year - 2002
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.70.9.5026-5035.2002
Subject(s) - anisomycin , p38 mitogen activated protein kinases , leishmania donovani , biology , mapk/erk pathway , leishmania , protein kinase a , macrophage , kinase , mitogen activated protein kinase , peripheral blood mononuclear cell , visceral leishmaniasis , microbiology and biotechnology , immunology , leishmaniasis , biochemistry , parasite hosting , in vitro , world wide web , computer science
Leishmania-induced macrophage dysfunctions have been correlated with altered signaling events. In this work, we report that SB203580, a specific inhibitor of p38 mitogen-activated protein kinases (MAPK), increases Leishmania donovani survival in human peripheral blood mononuclear macrophages. Consistent with this finding, activation of p38 and c-jun N-terminal kinase (JNK) MAPK signaling pathways by anisomycin significantly reduced parasite survival within these cells. However, the majority of the effect was seen in a 50% reduction in the percentage of macrophages infected, with little effect on the highly infected macrophages. The observed effect was likely to be due to the p38 MAPK pathway since SB203580 was able to completely reverse the effect of anisomycin. These findings suggest that the previously reported p38 MAPK inhibition by Leishmania infection may be partially overcome by anisomycin. Similar effects were observed in pretreated macrophages or in treatment of infected macrophages. These results suggests that p38 MAPK activation may have a potential therapeutic value in the treatment of visceral leishmaniasis.