1998 Fiscal Year Final Research Report Summary
Transmembrane signaling system concerning super oxide production
| Project/Area Number |
08670937
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Hokkaido University |
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Principal Investigator |
KOIZUMI Hiroko Medical Hospital, Hokkaido Univ.Lec., 医学部・附属病院, 講師 (60113552)
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| Project Period (FY) |
1996 – 1998
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| Keywords | keratinocyte / superoxide / calcium / protein kinase C / H202 |
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| Research Abstract |
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 trans-urocanic acid in the epidermis naturally occurring on exposure to UV irradiation. The mechanism by which cis-urocanic acid alters the immune system is not fully clarified. Urocanic acid acts through different mechanisms, perhaps via histamine or histamine-like receptors. Histamine stimulation of keratinocytes induces activation of adenylate cyclase to accumulate cyclic AMP and an increase of 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. The alterations of 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 cyclic AMP accumulation by histamine. Keratinocyte growth was not affected by cis-urocanic acid. Cis-urocanic acid did not induce an increase of intracellular Ca2+. Cis-urocanic acid attenuated the histamine induced increase in intracellular Ca2+ but not that induced by epinephrine. The effects of cis-urocanic acid on keratinocytes are revealed through modulation of effects of histamine.
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