Cadmium is not a redox-active metal like iron, copper, or chromium
but has been shown to stimulate the production of reactive
oxygen species (ROS) [37,38]. It was recently shown that cadmium
triggers production of ROS by inducing NADPH oxidase activity
leading to induction of signaling pathways such as STAT3 [39].
Our data shows that addition of DPI reduces Erk1/2 phosphorylation
and inhibits cadmium-induced secretion of IL-8 by HBE cells.
These results suggest that cadmium activates MEK/Erk1/2 pathway
via induction of NADPH oxidase and that activation of the MEK/
Erk1/2 pathway by cadmium is downstream of induction of
NADPH oxidase. However, DPI can also inhibit other electron transporters
such as nitric oxide synthase and xanthine oxidase [40].
Taken together, these results suggest that cadmium induces secretion
of IL-8 via production of ROS that is upstream of the MEK/
Erk1/2 MAPK pathway, and curcumin could prevent cadmium-induced
secretion of IL-8 by inhibiting activation of Erk1/2. The fact
that the antioxidant curcumin prevented cadmium-induced secretion
of both IL-6 and IL-8 by airway epithelial cells suggests that
curcumin could be a good therapeutic agent to prevent airway
inflammation due to cadmium inhalation.