Inhalation is an important route of Cadmium (Cd) exposure, and the lung is considered to be one of the main target organs of Cd toxicity, which is present in both air pollution and cigarette smoke. Pulmonary inflammation seems to be involved in development of many lung diseases also in Cd toxicity. In the present study, we aimed to evaluate effect of different dosages of Cd (1–100 mM) in normoxic, hypoxic and inflammatory conditions in normal and midkine overexpressed rat alveolar macrophage cell line NR8383. Midkine expression was controlled by RT-PCR. Total/phospho Nfkb, Ikb, p38/MAPK levels measured in cell lysates and midkine, TNF-a and IL-6 levels were evaluated by ELISA. K. Pneumonia LPS (10 mg/ml) stimulation induced NFkB activation, TNF-a and IL-6 secretions. Similar results were observed with TNF-a and midkine. Midkine overexpressed cells showed higher inflammatory response and TNF-a secretion. Our results showed that Cd at fairly low concentrations (1–2.5 mM) induced inflammation via p38/MAPK and NFkb activation and results in an increased secretion of cytokines in rat alveolar macrophage cell line (p<0.05). Cd causes cytotoxicity and suppresses inflammatory responses in a dose and time dependent manner. In conclusion, our results suggest that inflammation may contribute in Cd-induced lung damage in lower dosages, midkine is one of the important mediators of immune function. Moreover, with increasing dose of Cd, cytokine secretion response of alveolar macrophages is inhibited. Cd exposure might be one of the causes of the immune supressor results of cigarette smoking.

This study was supported by TUBITAK-BMBF (SBAG108S262).