Open AccessMitogen‐activated protein kinases regulate Mycobacterium avium ‐induced tumor necrosis factor‐α release from macrophages
Author(s) -
Bhattacharyya Asima,
Pathak Shresh,
Kundu Manikuntala,
Basu Joyoti
Publication year - 2002
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2002.tb00605.x
Subject(s) - tumor necrosis factor alpha , p38 mitogen activated protein kinases , biology , mapk/erk pathway , macrophage , kinase , microbiology and biotechnology , cytokine , peripheral blood mononuclear cell , protein kinase a , mitogen activated protein kinase , secretion , immunology , in vitro , biochemistry
Tumor necrosis factor‐α (TNF‐α) is one of the key cytokines elicited by host macrophages upon challenge with pathogenic mycobacteria. Infection of human peripheral blood mononuclear cells or the murine macrophage cell line J774A–1 with Mycobacterium avium induced activation of the mitogen‐activated protein kinases (MAPKs) ERK1/2, p38 and c‐Jun N‐terminal kinase. U0126, an MEK‐specific inhibitor, abrogated M. avium ‐induced TNF‐α secretion. Transfection of cells with dominant‐negative MEK1 led to the suppression of TNF‐α release in M. avium ‐challenged macrophages. M. avium activated p38 MAPK and use of the p38 MAPK inhibitor, SB203580, revealed that the p38 signaling pathway negatively regulates activation of ERK1/2 and release of TNF‐α. Taken together, these results provide evidence that M. avium ‐induced TNF‐α release from macrophages depends on an interplay between the ERK1/2 and the p38 MAPK signaling pathways.