Modulation of skin cell functions by transforming growth factor-beta1 and ACTH after ultraviolet irradiation

Abstract

The adaptive responses in skin to ultraviolet (UV) radiation include increased cornification of keratinocytes and increased synthesis and distribution of melanin by melanocytes.The possible involvement of paracrine factors in the generation of these responses was studied in a novel twostage culture model. Human melanocytes or keratinocytes were first irradiated or sham-irradiated and then the conditioned media collected from these cells after 24 h were used to treat unirradiated skin cells.Immunofluorescent staining for transforming growth factor (TGF)-1 was increased in UV-irradiated keratinocytes compared with sham-irradiated cells. Increased TGF-1 was also detected in the culture media of irradiated keratinocytes. Treatment of unirradiated keratinocytes with conditioned media collected from UVirradiated keratinocytes resulted in increased absolute numbers and percentages of cornified envelopes per well compared with treatment with conditioned media from sham-irradiated keratinocytes. The magnitude of this effect increased with increased dose of initial irradiation. The effects of conditioned media from UVR-treated cells were mimicked by authentic TGF-1. Treatment of conditioned media from irradiated cells with an antibody shown to neutralise the effects of TGF-1 but not with a non-immune antibody of similar isotype, abolished this bioactivity of the conditioned media from UV-irradiated cells. Immunofluorescent staining for ACTH was also increased in UV-irradiated keratinocytes. Conditioned media from UV-irradiated keratinocytes increased tyrosinase activity of unirradiated melanocytes, an effect which was mimicked by authentic ACTH. This bioactivity of conditioned media from irradiated keratinocytes was abolished in the presence of an antibody which neutralised the activity of ACTH but not MSH. These results provide evidence to support the involvement of TGF-1 and ACTH in the cornification and pigmentary responses respectively of skin cells after UV exposure.

Skin cancer prevention: A possible role of 1,25dihydroxyvitamin D3 and its analogs

“…Even though the data here and in our earlier report [9] show that application of 1,25(OH) 2 D 3 immediately post-UVR is photoprotective, the time course of production indicates that the Vitamin D hormone could thus not protect from the exposure UVR which produced it. This is also true for the better known endogenous photoprotective mechanisms of increased cornification and increased pigmentation [27,28]. Both of these adaptive responses take several hours to become fully effective, except for immediate pigment darkening, which is transient.…”

In vivo relevance for photoprotection by the vitamin D rapid response pathway

“…Because of this long time-course, it is unlikely that the 1,25(OH) 2 D 3 produced locally in skin protects from the UVR exposure responsible for its production. It is more likely that the locally produced vitamin D compounds protect from further UVR exposure, as is the case for UVR-induced increases in cornification and pigmentation [15,16]. Overirradiation products have some structural similarities to the rapid-acting agonists [3] and it is possible to speculate that these compounds may also contribute to the photoprotective effect.…”

Brain-Skin Connection: Stress, Inflammation and Skin Aging

“…Since CRH down-regulates IL-18 in keratinocytes [40], IL-18 may participate in the negative feedback loop to regulate HPA axis activity. In melanocytes ACTH stimulates proliferation and melanogenesis with a similar effect of α-MSH [41, 42]. Endogenous ACTH can stimulate hair growth in mouse model [43].…”