Hexavalent Chromium Influences Inflammatory Cytokines in Human Lung Cells

Chromium compounds are widely used industrial chemicals and are also recognized human carcinogens. In the occupational setting, hexavalent chromium Cr(VI) enters the human body via inhalation and dermal absorption. Chronic exposure to Cr(VI) may increase the risk for developing lung diseases among susceptible individuals by activating several soluble biochemical mediators of inflammation. We hypothesize that subchronic exposure to low doses of Cr(VI) induces cellular damage and activates mediators of inflammation. In the present study, we addressed the question on (a) whether hexavalent chromium alters the architecture of normal lung cells causing cytotoxic effects at low doses and, (b) whether the positive entry of Cr(VI) into the cell nucleus alters the transcription of genes involved in the process of inflammation. Using normal human lung cells we demonstrate that a low doses of Cr(VI) induces damage to the cell membrane. Total RNA extracted from lung cancer cells (A549) exposed to chromium was used for transcriptional regulation of mediators of inflammation using real time RT-PCR analysis. We determined an increase in the level of expression of IL-6, IL-10, TNF-a and COX-2. While there was no change in the expression of IL-8, IL-12, Cox-1, FGFR-1 and GADPH, MMP-2 gene was down regulated.Chromium exposed cells showed an increase in the nuclear level of NF-kBp65 protein and further studies are in progress to determine the DNA binding activity of NF-kB. Conclusion: Normal and lung cancer cells exposed to low doses of Cr(VI) showed activation of major pro-inflammatory factors compared to the control cells.