title: Mycobacterium tuberculosis-induced expression of Leukotactin-1 is mediated by the PI3-K/PDK1/Akt signaling pathway.
abstract: Chemokines function in the migration of circulating leukocytes to regions of inflammation, and have been implicated in chronic inflammatory conditions including mycobacterial infection. We investigated whether Leukotactin-1 (Lkn-1), a novel member of the CC-chemokines, is involved in the immune response of macrophages against Mycobacterium 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.
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, 220-710, Korea.
authors.forename: Jang-Eun
authors.initials: JE
authors.lastname: Cho
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Kim
authors.forename: Sangjung
authors.initials: S
authors.lastname: Park
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002633:Chemotaxis; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C108814:CCL15 protein, human; C000631429:PDK1 protein, human