HSP110 expression is induced by cadmium exposure but is dispensable for cell survival of mouse NIH3T3 fibroblasts.

The effects of cadmium exposure on the expression of HSP110 were examined in mouse NIH3T3 fibroblasts. Following exposure to cadmium chloride, the level of HSP110 and HSP70 proteins increased after 3h and remained elevated at 24h. Similarly, their mRNA levels increased markedly in response to cadmium exposure. Treatment with 10µM mercury chloride, another toxic metal compound, also induced expression of HSP110; however, HSP110 expression was not induced in cells exposed to the same concentration of manganese chloride, zinc chloride, or lead chloride for 6 or 24h. Silencing of HSP110 expression using short-interference RNA did not affect cadmium-induced cellular damage. These results show that cadmium exposure induces the expression of high molecular weight chaperone HSP110 as well as the well-known HSP70, but indicate that HSP110 does not play a major role in cell survival following cadmium exposure.

Fluoride-induced cyclooxygenase-2 expression and prostaglandin E2 production in A549 human pulmonary epithelial cells.

To clarify the mechanisms of fluoride-induced airway diseases, we examined the expression of cyclooxygenase-2 (COX-2), an important mediator of airway inflammation, in A549 human pulmonary epithelial cells treated with sodium fluoride (NaF). Following exposure to 5mM NaF, COX-2 protein and COX-2 transcript increased markedly. However, no change was observed in COX-1 expression. NaF-induced accumulation of COX-2 transcript was abolished by actinomycin D, but not cycloheximide. The level of prostaglandin E(2), a major product of COX enzymes, increased in response to NaF exposure, and its production was abolished by the selective COX-2 inhibitor NS-398. Phosphorylated forms of mitogen-activated protein kinases (MAPKs)-including extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase, and p38-increased after NaF exposure, while treatment with the MAPK/ERK kinase inhibitor U0126 and the p38 inhibitor SB203580 markedly suppressed COX-2 expression. Furthermore, NaF-induced COX-2 expression was markedly suppressed by the Src family kinase (SFK) inhibitor PP2, but only partially suppressed by the epidermal growth factor receptor (EGFR) inhibitor PD153035. These results suggest that NaF induces COX-2 expression by transcriptional up-regulation via p38 and ERK pathways, at least in part, and that SFKs may be upstream tyrosine kinases responsible for NaF-induced COX-2 expression in A549 cells.