Endothelin-1 of Keratinocyte Origin Is a Mediator of Melanocyte Dendricity

Abstract

Melanocytes synthesize melanin and transfer it to keratinocytes via dendritic processes. Keratinocytes are known to produce constitutively several factors, including endothelin-1 (ET-1), that together affect melanocyte proliferation, migration, melanogenesis, and dendrite formation. After ultraviolet (UV) irradiation, synthesis and secretion of ET-1 are up-regulated in keratinocytes. Because UV irradiation of skin is known to be associated with increased melanocyte dendricity, and because medium conditioned by UV-irradiated keratinocytes (UV-KCM) induces melanocyte dendricity to a greater degree than does baseline keratinocyte-conditioned medium (KCM), we investigated whether ET-1 promotes melanocyte dendricity. ET-1, originally recognized as a vasoconstrictive peptide, has recently been shown to stimulate melanocyte proliferation and tyrosinase activity. We now report that ET-1 supplementation of cultured melanocytes significantly increases the percentage of dendritic melanocytes, as well as dendrite length, in a dose-dependent manner. Moreover, UV-KCM was found to contain over 25-fold more ET-1 than KCM, and ET-1 supplementation of KCM induced melanocyte dendricity comparable to that induced by UV-KCM. Further, melanocyte dendricity induced by UV-KCM was significantly inhibited by the addition of anti-ET-1 monoclonal antibody to the medium, suggesting that the UV-KCM effect on melanocyte dendricity is mediated largely through ET-1. Our findings suggest that in the skin, ET-1 of keratinocyte origin promotes melanocyte dendricity in response to UV irradiation.

Behavioral differences between donor site-matched adult and neonatal melanocytes in culture

“…In a preliminary in vivo study, we were not able to find any significant differences between melanocytes from the two age groups when stained with dopa, NKI-beteb or S100 (data not shown). Considering the positive correlation between melanin formation and dendricity suggested by previous studies (Hara et al 1995;Nakazawa et al 1993), the findings seem to conflict. However, our findings agree with those of a previous study indicating that adult and neonatal melanocytes respond similarly to melanogenic stimulation by CT and IBMX (Abdel-Malek et al 1994).…”

“…Through dendritic processes, melanocytes transfer melanosomes into neighboring keratinocytes. Accordingly, melanocyte dendricity is a crucial factor in epidermal pigmentation (Hara et al 1995;Mosher et al 1993). This close relationship between melanocyte dendricity and pigmentation in vivo is supported by previous experimental findings showing that dendrite formation by cultured melanocytes correlates very well with melanogenesis (Hara et al 1995;Nakazawa et al 1993).…”

“…Accordingly, melanocyte dendricity is a crucial factor in epidermal pigmentation (Hara et al 1995;Mosher et al 1993). This close relationship between melanocyte dendricity and pigmentation in vivo is supported by previous experimental findings showing that dendrite formation by cultured melanocytes correlates very well with melanogenesis (Hara et al 1995;Nakazawa et al 1993). It has been suggested that dendricity and melanogenesis of melanocytes are increased by exposure to ultraviolet radiation (Friedmann and Gilchrest 1987;Jimbow et al 1993), prostaglandin E 2 (Tomita et al 1987), leukotriene-C 4 (Tomita et al 1992), cAMP inducers (Halaban et al 1983;Nakazawa et al 1993), nerve growth factor (Yaar et al 1994), endothelin-l (Hara et al 1995), and nitric oxide (Romero-Graillet et al 1997).…”

Cyclic AMP a Key Messenger in the Regulation of Skin Pigmentation

“…Among keratinocyte-secreted factors, which induce melanocyte activation, we find prostaglandins PGE2 (32), a-MSH and ACTH (33), endothelin-1 (34,35) and NO (20). a-MSH, ACTH and PGE2 activate the cAMP pathway in melanocytes, while NO activates the cGMP-dependent signaling events.…”

Differentiation-inducing activity of lupane triterpenes on a mouse melanoma cell line

“…In response to hormones and UV irradiation, melanin pigments are synthesized in melanosomes, which are transferred from the tips of melanocyte dendrites to the surrounding keratinocytes to protect against UV damage or carcinogenic effects (Boissy 2003;Okazaki et al 1976;Seiberg 2001). Studies have demonstrated that the dendritic outgrowth of melanocyte/melanoma cells is promoted by UV irradiation, cAMP-elevating agents and growth factors, as well as by the induction of melanogenesis; therefore, dendrites are recognized as a morphological indicator of melanocyte/melanoma cell differentiation (Hara et al 1995;Yoshida et al 2000). We investigated the formation of dendrites in B16 2F2 cells incubated with compound 1.…”