Kazumi Iwasaki

UV-induced apoptosis in rat skin

Sunburn cells appear in the epidermis after UVB irradiation and are histologically suggested to be keratinocytes undergoing apoptosis. We here show a known biochemical process of apoptosis, genomic DNA fragmentation, in rat skin. UVB irradiation induced sunburn cells in the epidermis of rat skin at a lower dosage and the cleavage of genome DNA to nucleosomal size units at dosages of more than 0.3 J/cm2. The fragmented DNA observed could be driven from the epidermis though the involvement of DNA in dermal cells cannot be neglected. PUVA treatment also induced sunburn cells and the fragmentation of genome DNA. The extent of DNA fragmentation by UVB irradiation was enhanced depending on the dosage and peaked at 12-24 h after the irradiation. The induction of the DNA fragmentation observed in this study indicates the presence of a common pathway related to the DNA damage-induced apoptosis in the skin, and might become a useful marker in the course of in vivo studies on the physiological role of apoptotic process in the skin.

Biphasic amyloidosis arising from friction melanosis.

A 40‐year‐old woman who had used nylon towels in the bath for about 10 years noticed hyperpigmentation on the prominent regions over the bones of the trunk and extremities. She also developed lichenoid papules with itching on her back. Histologically, both the pigmented and the papular lesions had amyloid deposits beneath the epidermis. In this case it is presumed that the papular lesions with amyloid (lichen amyloidosus) developed initially from friction melanosis which became macular pigmented lesion (macular amyloidosis). The etiologic factor of these sequential pathologic changes is considered to be repeated scrubbing with nylon towels.

Involvement of caspases in apoptosis induced by ultraviolet B irradiation in A431 human epithelioid tumor cells.

Six hours after ultraviolet B (UVB) irradiation (11.6 mJ/cm2), the viability of A431 cells decreased, and, at the same time, fragmentation of genomic DNA into nucleosomal units was observed. Z‐Asp‐CH2‐DCB (100 μM), an inhibitor of interleukin‐1 β‐converting enzyme (caspase‐1 ) and caspase‐1‐like proteases, markedly inhibited UVB‐induced cell death and DNA fragmentation. Both YVAD‐CMK, an inhibitor of caspase‐1, and DEVD‐CHO, an inhibitor of caspase‐3, moderately inhibited the UVB‐induced cell death. A combination of YVAD‐CMK and DEVD‐CHO acted additionally in inhibiting cell death. These observations suggest strongly the cooperative involvement of caspases in the apoptosis induced in A431 cells by UVB.

Effect of RU 486 on the atrophogenic and antiinflammatory effects of glucocorticoids in skin

Clobetasol-17-propionate (CP), a synthetic glucocorticoid (GC), reduced skin thickness in rats. Both the subcutaneous injection and topical applications of RU 486 counteracted CP-induced reduction in skin thickness. Topical application of the CP cream completely inhibited the ear edema produced by croton oil. A less potent GC, hydrocortisone-17-butyrate, also inhibited ear edema. This antiinflammatory effect was not abolished by the subcutaneous injection or topical application of RU 486. These observations suggest that GC-induced skin atrophy is mediated by glucocorticoid receptors (GRs), while the inhibition of croton oil-induced inflammation by GC is primarily related to the direct effects of GC, which are not mediated by GRs. Our findings suggest that RU 486 inhibits the atrophogenic effect of GCs without interfering with their antiinflammatory effect. Dissociation of antiinflammatory and atrophogenic activity of GC seems favorable in treating inflammatory skin diseases lacking epidermal proliferation.