c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) are involved in Mycobacterium tuberculosis-induced expression of Leukotactin-1.

Abstract

Leukotactin(Lkn)-1 is a CC chemokine and is upregulated in macrophages in response to Mycobacterium tuberculosis (MTB) infection. We investigated whether mitogen-activated protein kinases (MAPKs) are involved in MTB-induced expression of Lkn-1. The up-regulation of Lkn-1 by infection with MTB was inhibited in cells treated with inhibitors specific for JNK (SP600125) or p38 MAPK (SB202190). Since the up-regulation of Lkn-1 by MTB has been reported to be mediated by the PI3-K/PDK1/Akt signaling, we examined whether JNK and/or p38 MAPK are also involved in this signal pathway. MTB-induced Akt phosphorylation was blocked by treatment with JNK- or p38 MAPK-specific inhibitors implying that p38 and JNK are upstream of Akt. In addition, treatment with the PI3-K-specific inhibitor inhibited MTB-stimulated activation of JNK or p38 MAPK implying that PI3-K is upstream of JNK and p38 MAPK. These results collectively suggest that JNK and p38 MAPK are involved in the signal pathway responsible for MTB-induced up-regulation of Lkn-1.

• Authors: Jang-Eu Cho, Sangjung Park, Sang-Nae Cho, Hyeyoung Lee, Yoon Suk Kim
• Journal: BMB reports (BMB Rep) Vol. 45 Issue 10 Pg. 583-8 (Oct 2012) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 23101513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Chemokines, CC
• Imidazoles
• Pyridines
• pyrazolanthrone
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole

Topics

• Anthracenes (pharmacology)
• Cell Line, Tumor
• Chemokines, CC (metabolism)
• Humans
• Imidazoles (pharmacology)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Mycobacterium tuberculosis (enzymology, metabolism)
• Phosphatidylinositol 3-Kinases
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyridines (pharmacology)
• Signal Transduction (drug effects)
• Tuberculosis (metabolism, pathology)
• Up-Regulation (drug effects)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)