Oral communication, CS13 / C56

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Ultraviolet radiation A and B regulate the neuroendocrine stress response system in melanocyte/keratinocyte co-cultures

SPEAKER C. Skobowiat #whois submiter ?
AUTHOR(s) C. Skobowiat, J.C. Dowdy, R.M. Sayre, R.C. Tuckey, A. Slominski

Mammalian skin expresses a local equivalent of the hypothalamic-pituitary-adrenal (HPA) axis which modulates internal homeostasis against the external environment. Epidermal cells expresses corticotropin releasing hormone (CRH) and proopiomelanocortin (POMC) which is further processed by proconvertase 1/3 (PC1/3) and 2 (PC2) to β-endorphin (β-END), adrenocorticotropin (ACTH) and melanocyte stimulating hormone (MSH), similar to the central axis. Since ultraviolet (UV) radiation (UVR) is a tissue-specific stressor for the skin, we investigated the steps involved in the induction of the CRH→CRH-R1→POMC→β-END/ACTH→MC2R→glucocorticoids (GC) responses to UVR. In our comparative studies we used UVA and UVB wavelengths and different doses of exposure. Experiments were performed with co-cultured keratinocytes/melanocytes, a reliable epidermal equivalent for which the method is well established in our laboratory. We have also employed real time PCR (RT-PCR), ELISA, Western blotting and immunohistochemistry (IHC) in our analyses. We found enhanced expression of the “upper arm” of the HPA axis (CRH, POMC-derived β-END and ACTH) after UVA and UVB exposure. However, the lower arm of the HPA axis (MC2R, CYP11A1, CYP11B1, HSD11B1 and cortisol) was stimulated only by UVB, with no marked effects from UVA radiation. The enhanced production of cortisol after UVB was followed by decreased expression of the GC receptor (GR), unlike for UVA where the nuclei of epidermal cells exhibited a strong immunofluorescent signal to GR. This study shows that UVR can stimulate the “local equivalent” of the HPA axis in the epidermis of the human skin in a dose and wavelength dependent way. The subsequent decrease in GR expressions may indicate an epidermal mechanism to attenuate the long-term immunosuppressive effects of cortisol by down-regulating the expression of its receptor, in order to restore the biological barrier.



Advertisement from our sponsor:
Astellas Pharma Worldwide

Université de Bordeaux 2 & Conseil Régional Aquitaine