Mycobacterium tuberculosis-Induced Expression of Leukotactin-1 Is Mediated by the PI3-K/PDK1/Akt Signaling Pathway

• Published in: Molecules and cells Vol. 29; no. 1; pp. 35 - 39
• Main Authors: Cho, Jang-Eun, Kim, Yoon-Suk, Park, Sang-Jung, Cho, Sang-Nae, Lee, Hye-Young
• Format: Journal Article
• Language: Korean
• Published: 2010
• Subjects: 3-phosphoinositide-dependent kinase 1; Mycobacterium tuberculosis; Akt; Leukotactin-1; phosphatidylinositol 3-kinase
• ISSN: 1016-8478; 0219-1032

Chemokines function in the migration of circulating leukocytes to regions of inflammation, and have been implicated in chronic inflammatory conditions including myco-bacterial infection. We investigated whether Leukotactin-1 (Lkn-1), a novel member of the CC-chemokines, is involved in the immune response of macrophages against Myco-bacterium tuberculosis (MTB). In PMA-differentiated THP-1 cells, MTB infection increased mRNA expression of Lkn-1 in a dose-dependent manner. Lkn-1 induction peaked 12 h after infection, then declined gradually and returned to its basal level at 72 h. Secretion of Lkn-1 was elevated by MTB infection. The increase in expression and secretion of Lkn-1 caused by MTB was reduced in cells treated with inhibitors of phosphatidylinositol 3-kinase (PI3-K), 3-phosphoinositide-dependent kinase 1 (PDK1) and Akt. MTB-induced Akt phosphorylation was blocked by treatment with a PI3-K inhibitor or a PDK1 inhibitor, implying that PI3-K, PDK1, and Akt are associated with the signaling pathway that up-regulates Lkn-1 in response to MTB. These results suggest that Lkn-1 is novel member of the group of chemokines that is released by macrophages infected with MTB.