|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1995 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1994 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1993 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Epidermal keratinocytes proiferate and differentiate to make stratum corneum. Many chemical mediators, hormones and peptides stimulate keratinocytes to induce phosphophatidylinositol metablism, alteration of intracellular free calcium, adenylate cyclase response activation. We elucidated that bradykinin, thrombin, substance P,beta-adrenarin, adenosine, and histamine induce increase of intracellular free calcium. These effects are mediated with synthesis of inositol 1,4,5-trisphosphate or adenylate cyclase activation. The importance of calcium as a second messenger is shown. Presence of membrane skeleton proteins such as spectrin, b-fodrin, 4.1 protein like proteins were detected immunologically and the alteration of their distribution in cultured keratinocytes and diseased skin were observed. A new technique was reported to detect peroxide produced from keratinocytes using dihydrorhodamine 123. Differentiation associated expression of nPKC eta and SPRR was demonstrated in normal and diseased skin. The expression and cornified envelope formation are considered to mediated by activation of nPKC eta.
Cross-talk among transmembrane signaling systems in keratinocytes, and drugs to influence these systems should be investigated. Abnormal keratinization and accerelation of proliferation are considered to closely realt to pathogenesis of psoriasis. The alteration of membrane signaling systems in psoriasis and the action mechanisms of the drugs used in therapy of skin diseases are under investigation.