Hexavalent Chromium-induced ROS Formation, Subsequent Akt, NF-κB, and MAPK Activation, and TNF-α, and IL-1α Production in Keratinocytes, Which Might Facilitate the Progression of Chromium Hypersensitivity

Abstract

PP-31-153 Background/Aims: Chromium (Cr) hypersensitivity is an important issue in occupational skin disease. When Cr(VI) enters the cell, it can be reduced to Cr(III), resulting in the formation of reactive oxygen species (ROS). By the effects of ROS, Cr(VI) could activate the Akt, NF-κB, and MAPK pathways. Cr(VI) could also stimulate the release of cytokines, such as TNF-α and IL-1α. The release of TNF-α and IL-1 is a central event in the progression of allergic contact dermatitis. Aims: We hypothesized that keratinocytes might be stimulated by Cr(VI), resulting in the formation of ROS, which activates the Akt, NF-κB, and MAPK pathways, increasing TNF-α and IL-1α production. Methods: In vitro, we used HaCaT cells exposed to Cr(VI) and monitored ROS formation and the activation of the Akt, NF-κB, and MAPK pathways, as well as the expression of TNF-α mRNA and the release of IL-1α. In vivo, we administered a Cr(VI) dermal injection to albino guinea pigs to observe the activation of the Akt, NF-κB, and MAPK pathways. Results: We found that, in HaCaT cells, Cr(VI) could increase ROS formation, activate the Akt, NF-kβ, and MAPK pathways, and increase the expression of TNF-α mRNA and the release of IL-1α. We also found that, in albino guinea pigs, a Cr(VI) injection could activate the Akt, NF-kβ, and MAPK pathways. Conclusion: These observations indicate that Cr(VI) could increase ROS formation, activate the Akt, NF-kβ, and MAPK pathways, and increase the expression of TNF-α mRNA and the release of IL-1α, which might facilitate the progression of chromium hypersensitivity.