The main physiological stimulus of melanogenesis is the ultraviolet radiation of solar light
which can act directly on melanocytes or indirectly through the release of keratinocyte-derived factors such as aMSH (a-melanocyte stimulating hormone), a potent inducer of melanogenesis both in vivo and in vitro (Levine et al., 1991; Hunt et al., 1994). The mechanism by which aMSH stimulates melanogenesis is now well established. This hormone binds to a speci®c melanocortin receptor (MC-1R) coupled to an as type G protein, resulting in the stimulation of adenylate cyclase activity and in an increase in cAMP levels. The cAMP pathway plays a pivotal role in the regulation of melanogenesis since the e#1113088;ect of aMSH can be mimicked by cAMP elevating agents including cholera toxin, forskolin and IBMX (O'Keefe and Cuatrecasas, 1974; Englaro et al., 1995). aMSH as well as other cAMP elevating agents increases the expression of melanogenic enzymes, in particular that of tyrosinase, through a transcriptional mechanism which involves micropthalmia a basic-helix-loop helix tissue speci®c transcription factor (Bertolotto et al., 1996).
TNFa, a pro-in #772;ammatory cytokine, is produced by many cell types, including macrophages, lymphocytes, ®broblasts and keratinocytes, in response to inflamma- tion, infection, and other environmental stresses (Tracey and Cerami, 1993; Kock et al., 1990). TNFa induces a heterogeneous array of biological e#1113088;ects. It may elicit cell proliferation, di#1113088;erentiation or apoptosis according to the cell type. TNFa, as a trimeric ligand, binds to TNF receptor R1 (p55) or R2 (p75). However, most of the biological responses of TNFa are thought to be mediated through TNF-R1 (Vandenabeele et al., 1995).
Forskolina XD
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