Cadmium Induced Apoptosis in MG63 Cells by Increasing ROS, Activation of p38 MAPK and Inhibition of ERK 1/2 Pathways.

BACKGROUND/AIMS: Cadmium (Cd) induces apoptosis in different kinds of cells, including osteoblasts, both in vivo and in vitro. However, little is known about the mechanisms by which Cd induces apoptosis. METHODS: In the present study, we used the human osteosarcoma cell line MG63, which has characteristics similar to human osteoblasts, as an in vitro model to determine the cellular mechanisms by which Cd induces apoptosis. RESULTS: We found that short-term exposure to CdCl2 induced apoptosis in MG63 cells. Furthermore, the incubation of cells with CdCl2 significantly increased the level of phosphorylated p38MAPK and significantly decreased the phosphorylation of ERK1/2 in a concentration-dependent manner. Additionally, the inhibition of the phosphorylation of p38 MAPK by SB202190 protected MG63 cells from Cd-induced apoptosis. The incubation of MG63 cells with the ERK1/2 inhibitor PD98059 significantly increased apoptosis in MG63 cells. CdCl2 also significantly increased the intracellular levels of ROS. N-acetylcysteine (NAC) significantly reduced ROS levels and reversed the effects of CdCl2 on MAPK signaling. CONCLUSION: Our results suggested that Cd induced apoptosis in MG63 cells by increasing ROS, activation of p38 MAPK and inhibition of ERK1/2 pathways.

Relationship between Helicobacter pylori infection and serum interleukin-18 in patients with carotid atherosclerosis.

BACKGROUND: Helicobacter pylori (H. pylori) infection stimulates the production of proinflammatory cytokines associated with the development of atherosclerosis. Levels of circulating interleukin-18 (IL-18) have been positively correlated with carotid intima-media thickness (IMT) and coronary plaque area and have identified IL-18 levels as important predictors of coronary events and cardiovascular mortality. This study aimed to examine the relationship between serum IL-18 and H. pylori-IgG antibody as a sign of H. pylori infection in patients with carotid atherosclerosis. METHODS: The carotid IMT, traditional atherosclerotic risk factors, levels of serum H. pylori-IgG and IL-18 were measured in 573 health checkup examinees. RESULTS: Serum IL-18 and H. pylori-IgG levels were significantly increased in subjects with increased IMT in comparison with those with normal IMT. In subjects with increased IMT, serum H. pylori-IgG was positively correlated with serum IL-18 (r = .402, p = .002), and the association was independent of traditional atherosclerotic risk factors (ß = 0.310, p < .001). CONCLUSIONS: In health checkup examinees with increased IMT, serum IL-18 and H. pylori-IgG were independently correlated and were significantly higher than in subjects with normal IMT.

Aspirin inhibits tumor necrosis factor-alpha-stimulated fractalkine expression in human umbilical vein endothelial cells.

BACKGROUND: Fractalkine is an important chemokine mediating local monocyte accumulation and inflammatory reactions in the vascular wall. Aspirin inhibits inflammatory cytokine expression closely related to atherosclerosis through the way independent of platelet and cyclooxygenase (COX). There has been no report about the effect of aspirin on fractalkine expression. We aimed to determine the fractalkine expression in human umbilical vein endothelial cell (HUVEC) stimulated by tumor necrosis factor (TNF)-alpha and the effect of aspirin intervention. METHODS: Six of 8 HUVEC groups received either different concentrations of aspirin (0.02, 0.2, 1.0, 5.0 mmol/L) or 40 micromol/L pyrrolidinecarbodithioc acid (PDTC) or 0.5 micromol/L NS-398. The other two groups were negative control and positive control (TNF-alpha-stimulated). After being incubated for 24 hours, cells of the 8 groups except the negative control one were stimulated with TNF-alpha (4 ng/ml) for another 24 hours. After that, the cells were collected for RNA isolation and protein extraction. RESULTS: Both mRNA and protein expressions of fractalkine in HUVEC were upregulated by 4 ng/ml TNF-alpha stimulation. Aspirin inhibited fractalkine expression in a dose-dependent manner at mRNA and protein levels. Nuclear factor-kappa B inhibitor, PDTC, effectively decreased the fractalkine expression. Fractalkine expression was not influenced by COX-2 selective inhibitor NS-398. COX-1 protein expression was not changed by either TNF-alpha stimulation or aspirin, PDTC, NS-398 intervention. Both mRNA and protein expression of COX-2 in HUVEC were upregulated by 4 ng/ml TNF-alpha stimulation. Aspirin decreased COX-2 expression in a dose-dependent manner at mRNA and protein levels. CONCLUSIONS: TNF-alpha-stimulated fractalkine expression is suppressed by aspirin in a dose-dependent manner through the nuclear factor-kappa B p65 pathway.