title: Curcumin inhibits 19-kDa lipoprotein of Mycobacterium tuberculosis induced macrophage apoptosis via regulation of the JNK pathway.
abstract: Recently, synthetic curcumin analogs are reported as potential active compounds against Mycobacterium tuberculosis (MTB). During the process of MTB infection, macrophages show increased apoptosis. The candidate virulence factors such as 19-kDa lipoprotein secreted by the MTB (P19) strongly influences macrophages by activation of Toll-like receptor 2 (TLR2) and mitogen-activated protein kinases (MAPKs). It has been reported that curcumin could affect the apoptosis of tumor cells via regulation of MAPKs. However, its effect on the P19-induced apoptosis of macrophages is unclear. This study investigates the effect of curcumin on the MAPKs signaling and apoptosis in human macrophages. The results showed that curcumin and P19 induced macrophage apoptosis in a time- and dose-dependent manner Low doses of curcumin (10 and 20 μM) protected macrophages from P19 induced apoptosis, accompanied by decreased production of cytokines and reduced activation of the c-Jun amino-terminal kinase (JNK) and p38 MAPK. The protective effect of curcumin on P19 induced apoptosis of macrophages were enhanced by treatment with the JNK-specific inhibitors, whereas SB203580, the inhibitor of p38 MAPK had no effect. Curcumin had no effect on the activity of extracellular signal-regulated protein kinase (ERK). Taken together, our data show that the JNK pathway, but not the p38 or ERK pathway, plays an important role in the protective effect of curcumin against P19 induced macrophage apoptosis, and regulation of the JNK pathway may partially elucidate the anti-tuberculosis activity of curcumin.
authors.affiliation: The Fourth Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, 463000 Xinxiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: M Y
authors.affiliation: The Second Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, 463000 Xinxiang, China.
authors.forename: Wang
authors.initials: W
authors.lastname: H L
authors.affiliation: The Second Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, 463000 Xinxiang, China.
authors.forename: Huang
authors.initials: H
authors.lastname: J
authors.affiliation: The Third Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, 463000 Xinxiang, China.
authors.forename: Shi
authors.initials: S
authors.lastname: G C
authors.affiliation: The Fourth Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, 463000 Xinxiang, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Y G
authors.affiliation: The Fourth Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, 463000 Xinxiang, China.
authors.forename: Wang
authors.initials: W
authors.lastname: J X
authors.affiliation: The Fourth Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, 463000 Xinxiang, China. Electronic address: xiue_xi721@126.com.
authors.forename: Xi
authors.initials: X
authors.lastname: X E
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D053760:Interleukin-23 Subunit p19 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D053760:Interleukin-23 Subunit p19; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: Apoptosis; Curcumin; Macrophages; Mycobacterium tuberculosis 19-kDa lipoprotein; c-Jun N-terminal kinase