Mycobacterium tuberculosis-induced expression of granulocyte-macrophage colony stimulating factor is mediated by PI3-K/MEK1/p38 MAPK signaling pathway

Members of the colony stimulating factor cytokine family playimportant roles in macrophage activation and recruitment toinflammatory lesions. Among them, granulocyte-macrophagecolony stimulating factor (GM-CSF) is known to be associatedwith immune response to mycobacterial infection. However,the mechanism through which Mycobacterium tuberculosis(MTB) affects the expression of GM-CSF is poorly understood.Using PMA-differentiated THP-1 cells, we found that MTBinfection increased GM-CSF mRNA expression in a dosedependentmanner. Induction of GM-CSF mRNA expressionpeaked 6 h after infection, declining gradually thereafter andreturning to its basal levels at 72 h. Secretion of GM-CSFprotein was also elevated by MTB infection. The increase inmRNA expression and protein secretion of GM-CSF caused byMTB was inhibited in cells treated with inhibitors of p38MAPK, mitogen-activated protein kinase kinase (MEK-1), andPI3-K. These results suggest that up-regulation of GM-CSF byMTB is mediated via the PI3-K/MEK1/p38 MAPK-associatedsignaling pathway. [BMB Reports 2013; 46(4): 213-218