Open AccessMycobacterium tuberculosis H37Rv induces monocytic release of interleukin‐6 via activation of mitogen‐activated protein kinases: inhibition by N ‐acetyl‐ l ‐cysteine
Author(s) -
Natarajan Palaniappan,
Narayanan Sujatha
Publication year - 2007
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2007.00256.x
Subject(s) - protein kinase a , biology , p38 mitogen activated protein kinases , mitogen activated protein kinase , mitogen activated protein kinase kinase , kinase , map kinase kinase kinase , map2k7 , ask1 , cyclin dependent kinase 2 , c raf , microbiology and biotechnology
The release of proinflammatory cytokines after mycobacterial infection is a host immune response that may be propitious or deleterious to the host. Elevated levels of interleukin (IL)‐6 are present in plasma of patients with active tuberculosis infection. The aim of this study was to investigate the role of mitogen‐activated protein kinases in the secretion of interleukin‐6 in THP‐1 cells and human primary monocytes that were infected with Mycobacterium tuberculosis H37Rv, and its regulation by N ‐acetyl‐ l ‐cysteine, a potential antimycobacterial agent. Exposure of THP‐1 human monocytes to M. tuberculosis H37Rv induced rapidly, in a time‐dependent manner, the phosphorylation of mitogen‐activated protein kinase kinase 3/6 and p38 mitogen‐activated protein kinase, accompanied by an upregulation of interleukin‐6. Using highly specific inhibitors of mitogen‐activated protein kinase kinase‐1, p38 mitogen‐activated protein kinase and nuclear factor‐κB, we found that extracellular‐signal regulated kinase 1/2, p38 mitogen‐activated protein kinase and nuclear factor‐κB were essential for M. tuberculosis H37Rv‐induced interleukin‐6 production in human primary monocytes. Pretreatment with N ‐acetyl‐ l ‐cysteine reduced, in a dose‐dependent manner, M. tuberculosis H37Rv‐induced activation of mitogen‐activated protein kinase kinase 3/6 and interleukin‐6 production in THP‐1 cells.