Chapter 20 - Silibinin Protects Ultraviolet B–Irradiated Skin by Balancing Apoptosis and Autophagy in Epidermis and Dermis

Abstract

Skin inflammation induced by ultraviolet B (UVB) irradiation is caused by epidermal cell death, accompanying damages of basement membrane and dermis in subbasement membrane region. Migration and chemotaxis of inflammatory cells, epidemic thickening, and erythema are characteristic for the skin inflammation or sunburn in short. It was found that dermal cells including migratory inflammatory cells showed retarded apoptosis by UVB irradiation, resulting in production and secretion of proinflammatory cytokines in higher amounts for prolonged time, substantially contributing to skin inflammation. Retarded apoptosis in dermis appeared to correspond with upregulation of autophagy in dermis. Therefore we hypothesize that UVB-irradiated skin became inflammatory by the synergistic interaction of upregulated apoptosis in epidermis (in association with lowered autophagy) with retarded apoptosis in dermis (in association with enhanced autophagy); briefly, balance of apoptosis and autophagy is reciprocal between dermis and epidermis. The present study examined the working hypothesis by measuring changes in apoptosis and autophagy levels in epidermis and dermis separated from the skin irradiated by UVB in the presence and absence of silibinin. We found that UVB irradiation caused imbalance of apoptosis and autophagy in epidermis and dermis from that of the dermis and epidermis prior to UVB irradiation. Furthermore, we found that silibinin readjusted the balance of apoptosis and autophagy in both epidermis and dermis to the skin state prior to UVB irradiation, demonstrating that silibinin plays dual roles in protecting skin inflammation caused by UVB irradiation. Since the balances of apoptosis and autophagy are opposite in epidermis and dermis under inflammatory conditions or noninflammatory conditions, there must be differential regulations in balancing. We thus examined the involvements of p53 and nuclear factor κB in the regulations of apoptosis and autophagy. Our tentative conclusions are as follows: Autophagy, which either enhances or retards apoptosis, is regulated by p53 both in dermis and in epidermis. Upregulated p53 downregulates the autophagy, and downregulated p53 activation upregulates the autophagy. Dual roles of silibinin are thus accounted for by downregulation of p53 leading to upregulation of autophagy in dermis and upregulation of p53 leading to downregulation of autophagy in epidermis. Sunscreen and antiinflammatory drugs have been used to minimize skin erythma caused by UV irradiation, even though they have only preventive efficacy but no reparative effect. Silibinin is effective for postinflammatory skin and thus a potential drug with a novel efficacy for protection of UVB-irradiated inflammation including sunburn and allergic diseases for human skin.