[The effects of curcumin on the 19 000 Mycobacterium tuberculosis protein-induced inflammatory and apoptotic reaction and the expression of p38 mitogen-activated protein kinases in WBC264-9C macrophages].

OBJECTIVE

By using the cell wall component of Mycobacterium tuberculosis 19 000 lipoprotein (P19) and curcumin (CUR) acting on the human macrophage cell line WBC264-9C, and by the blocking of the p38 mitogen-activated protein kinases (p38 MAPK) signaling pathway, we wanted to investigate the effect of curcumin on P19-induced inflammatory responses and apoptosis in human macrophages and the potential underlying molecular mechanisms.

METHODS

P19 and CUR were used to stimulate human macrophages for 48 h. Their effects on growth inhibition and on apoptosis in macrophages were observed. The combination effect of CUR with P19 on the expression of IL-1β, IL-6, TNF-α, STAT3, P53, Bax, Bcl2 and phspho-p38 MAPK levels were also observed. By using the antagonist of p38 MAPK, the effect of CUR on P19-induced expression of inflammatory cytokines and apoptotic proteins were investigated.

RESULTS

Twenty and 40 µmol/L of CUR inhibited the growth of macrophages by (10.1 ± 2.3)% and (19.0 ± 2.7)%. The growth inhibition rate of macrophages in the controls, P19 and P19+CUR treated groups were (6.7 ± 4.2)%, (45.4 ± 3.6)% and (32.1 ± 3.0)%, respectively. The P19-induced growth inhibition was significantly attenuated by CUR treatment (q = 9.75, P < 0.01). The expression of IL-1β, IL-6, TNF-α and STAT3 mRNA (13.2 ± 2.7, 33.5 ± 1.1, 3.3 ± 2.2, 0.9 ± 1.7) were significantly lower than P19-treated groups (21.8 ± 3.5, 14.3 ± 1.4, 6.1 ± 3.6, 4.5 ± 3.4) (q values were ranged from 7.18 to 3.22, all P < 0.05). Furthermore, P53 protein (94.3 ± 0.2; q = 7.05, P < 0.01) and Bax (70.8 ± 8.7; q = 7.66, P < 0.01) levels were decreased in CUR+P19 group as compared with P19 group (320.2 ± 0.2 and 182.6 ± 1.2). Blockade of p38 MAPK accompanied with CUR and P19 induced significantly lower levels of IL-6 mRNA (34.9 ± 1.5, q = 2.36, P < 0.05) and Bax/Bcl2 protein (0.36 ± 0.09; q = 3.50, P < 0.05) expression, as compared with the controls (69.9 ± 1.8 and 0.71 ± 0.11).

CONCLUSIONS

P19 increased the expression of inflammatory cytokines and promoted the apoptosis of macrophages possibly through the activation of p38 MAPK signaling pathway. Low concentration of curcumin may play a protective effect against P19-induced immune responses by inhibiting the p38 MAPK pathway in macrophages.