Koizumi H, Shimizu T, Nishino H, Ohkawara A
Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
Arch Dermatol Res. 1998 May;290(5):264-9. doi: 10.1007/s004030050302.
UVB irradiation causes suppression of delayed hypersensitivity. Various photoreceptors and mediators of these changes have been proposed, one of which is cis-urocanic acid formed from the naturally occurring trans-urocanic acid in the epidermis on exposure to UV irradiation. The mechanism by which cis-urocanic acid alters the immune system is not fully clarified, but it acts through different mechanisms, perhaps via histamine or histamine-like receptors. Histamine stimulation of keratinocytes induces activation of adenylate cyclase leading to an accumulation of cyclic AMP and an increase in intracellular Ca2+. Thus we investigated the effects of cis-urocanic acid on these transmembrane signaling systems in keratinocytes. Normal human keratinocytes were cultured in serum-free KGM medium. Cyclic AMP was measured by radioimmunoassay. Alterations in intracellular Ca2+ in single living keratinocytes were measured using an inverted fluorescence microscope and an ARGUS-200/CA digital imaging system. Cis-urocanic acid itself did not induce adenylate cyclase activation in cultured normal human keratinocytes. Cis-urocanic acid inhibited histamine-induced cyclic AMP accumulation. It did not affect keratinocyte growth, and did not induce an increase in intracellular Ca2+, but did attenuate the histamine-induced increase in intracellular Ca2+ but not that induced by epinephrine. Cis-urocanic acid acts on keratinocytes via modulation of the effects of histamine.
