Curcumin inhibits 19-kDa lipoprotein of Mycobacterium tuberculosis induced macrophage apoptosis via regulation of the JNK pathway
| Autor: | Guangcan Shi, Jiaqin Wang, Wan Yonggan, Helin Wang, Huang Jian, Xiu'e Xi, Mingying Li |
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| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
Curcumin Kinase MAP Kinase Signaling System p38 mitogen-activated protein kinases Macrophages Biophysics Apoptosis Cell Biology Mycobacterium tuberculosis Biochemistry p38 Mitogen-Activated Protein Kinases Cell biology TLR2 chemistry.chemical_compound chemistry Gene Expression Regulation Interleukin-23 Subunit p19 Humans Protein kinase A Receptor Molecular Biology Cells Cultured |
| Zdroj: | Biochemical and biophysical research communications. 446(2) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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