Stress Response of Human Cell Lines to Ultraviolet B Irradiation

Abstract

Increased expression of a specific set of genes as a consequence of extracellular stress is typically observed in all organisms. Heat shock proteins (hsps) are a set of evolutionarily conserved proteins, some constitutively expressed and others induced in response to physiological and environmental stresses(1). However,changes in expression of many stress-inducible genes often occur under conditions that are ultimately lethal to the cell. UVB has been reported to initiate a variety of hsp expression in mouse keratinocytes (2), as well as the induction of hsp72 in cultured human fibroblasts (3) and keratinocytes (4). This stress response may be extremely important in the protection of human skin from UV-induced injury. The ability of UVB to induce the expression of hsps in human skin cell is important because these proteins are critical for the survival of cells exposed to a variety of environmental stresses. In particular, a suboptimal stress response in skin cells may predispose skin to melanoma development and photoageing. Nevertheless, heat shock protein function offers a potential therapeutic target for modulation of UV-irradiation skin carcinogenesis and ageing.Reactive oxygen species (ROS) have been implicated in UVB induced damage to skin. The endogenous antioxidant capacity of skin, including nonenzymatic low molecular weight antioxidants and enzymes, may be a major determinant in its response to UVB oxidative mediated damage. Antioxidants may also modulate the expression of genes whose products are involved in carcinogenesis, ageing and inflammation (5). NF-KB may be a central target for oxidants in the UV response but signaling pathways involved in the antioxidant protection against UVB irradiation are not well understood. Large-scale gene expression analysis with eDNA arrays, provide the opportunity to observe the broad effects of UVB-irradiation and antioxidants on signaling pathways. The results presented here address the hypothesis that antioxidants may ameliorate UV-induced skin damage through the concerted modulation of gene expression.