Figure 6.

Differential and overlapping phenotypic effects secondary to activation of corticotropin-releasing hormone receptor 1 (CRHR1) in human keratinocytes and melanocytes. A: activation of CRHR1 in normal epidermal keratinocytes and melanocytes, respectively stimulates and inhibits NF-κB activity. In immortalized HaCaT keratinocytes, CRF both inhibits and stimulates NF-κB activity, depending on the environmental context (171). B: in keratinocytes, activation of CRHR1 directly inhibits proliferation and stimulates differentiation and immune activity via stimulation of NF-κB. This enhances protective epidermal barrier function. In melanocytes, CRHR1 directly and indirectly [through proopiomelanocortin (POMC) peptides] stimulates differentiation and melanin production leading to enhancement of protective barrier function. In contrast to keratinocytes, there is an indirect (through POMC peptides) inhibition of NF-κB with subsequent suppression of immune activity, which can be amplified by production of cortisol by melanocytes. Reprinted from Ref. 78 with the permission of the publisher.