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

• Published in: BMB reports 2013, 46(4), , pp.213-218
• Main Authors: Cho, J.E., 1Daegu Health College, Daegu, Republic of Korea, Park, S.J., Yonsei University,Wonju, Republic of korea, Lee, H.Y., Yonsei University,Wonju, Republic of korea, Cho, S.N., Yonsei University College of Medicine, Seoul, Republic of Korea, Kim, Y.S., Yonsei University,Wonju, Republic of korea
• Format: Article
• Language: English
• Subjects: GM-CSF; GM-CSF, MEK1; MEK1; MYCOBACTERIUM TUBERCULOSIS; p38 MAPK; PI3-K; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2013.46.4.200

Members of the colony stimulating factor cytokine family play important roles in macrophage activation and recruitment to inflammatory lesions. Among them, granulocyte-macrophage colony stimulating factor (GM-CSF) is known to be associated with 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 MTB infection increased GM-CSF mRNA expression in a dosedependent manner. Induction of GM-CSF mRNA expression peaked 6 h after infection, declining gradually thereafter and returning to its basal levels at 72 h. Secretion of GM-CSF protein was also elevated by MTB infection. The increase in mRNA expression and protein secretion of GM-CSF caused by MTB was inhibited in cells treated with inhibitors of p38 MAPK, mitogen-activated protein kinase kinase (MEK-1), and PI3-K. These results suggest that up-regulation of GM-CSF by MTB is mediated via the PI3-K/MEK1/p38 MAPK-associated signaling pathway.