Figure 8.

Differential phenotypic effects of CRF1 signaling in keratinocytes and melanocytes with secondary impact on skin barrier formation. In keratinocytes, CRF1 directly inhibits proliferation and stimulates differentiation plus stimulation of immune activity via stimulation of NF-κB. This enhances protective epidermal barrier function. In melanocytes, CRF1 directly and indirectly (through POMC peptides) stimulates differentiation and melanin production, and the latter enhances protective barrier function. In contrast to keratinocytes, CRF1 signaling leads indirectly (through POMC peptides) to inhibition of NF-κB with subsequent suppression of immune activity. This immunosuppressive effect can be amplified by production of cortisol by melanocytes.