α-Melanocyte Stimulating Hormone Downregulates Differentiation-Driven Heat Shock Protein 70 Expression in Keratinocytes

Abstract

Heat shock proteins are versatile tools engaged in several cellular functions. In particular, the stress-inducible 70-kDa heat shock protein (hsp70) not only confers protection on cells but also is involved in the regulation of the production of cellular stress response mediators including cytokines. In addition to cytokines, neurohormones such as alpha-melanocyte stimulating hormone (alphaMSH) were recently found to be potent mediators of inflammatory and immune responses. Thus, the current study was performed to investigate the role of alphaMSH in the expression of hsp70 in a human keratinocyte cell line (HaCaT). Proliferation and differentiation of HaCaT cells are known to be regulated by changing extracellular Ca2+ concentrations. HaCaT cells induced to differentiate in high Ca2+ medium (1.5 mM) were found to express higher levels of hsp70 protein than cells grown under low Ca2+ conditions. Moreover, differentiated HaCaT cells were markedly more resistant to oxidative stress than undifferentiated control cells. alphaMSH significantly suppressed hsp70 expression in a concentration-dependent manner in differentiated HaCaT cells but had only a minor effect on undifferentiated cells. Upon treatment with alphaMSH, HaCaT cells grown in high Ca2+ medium were rendered more sensitive to oxidative stress, which significantly decreased their survival rate. These findings indicate that alphaMSH, which is released by keratinocytes in an autocrine fashion following injurious stimuli such as tumor promoters or ultraviolet light, is able to regulate the cells' cytoprotective protein equipment.