The protective effect of curcumin against the 19­kDa Mycobacterium tuberculosis protein-induced inflammation and apoptosis in human macrophages.

ABSTRACT

The Mycobacterium tuberculosis 19-kDa lipoprotein (P19) is both cell wall-associated and secreted and is a candidate virulence factor that could cause the apoptosis of human macrophages infected with M. tuberculosis. P19 induces TLR2 activation, resulting in the upregulation of death receptors and ligands, followed by a death-receptor signaling cascade. The mechanisms by which P19 induces macrophage apoptosis are not fully characterized. Curcumin, a natural polyphenol, exhibits a variety of pharmacological effects such as antioxidant, anti-inflammatory and antitumor properties. In the present study, we investigated the effect of curcumin on P19-induced apoptosis in human macrophage cells and the underlying mechanisms. The results showed that both P19 and curcumin inhibit the growth of macrophages in a dose- and time-dependent manner. A low dose of curcumin (10 or 20 µM) attenuated both the macrophage cell growth inhibition and the increase in the expression of IL-6 and TNF-α induced by P19. Curcumin also decreased the phosphorylation of JNK and p38 that were induced by P19. However, JNK but not p38 inhibitors reversed the effect of P19 on the growth inhibition of macrophages. These data suggest that curcumin may protect macrophages from P19-induced cell apoptosis via a TLR2-mediated JNK-dependent pathway.