Human Keratinocytes Express Functional Α-MSH (Mc1-R) Receptors

Curry, Jonathan L.; Pinto, Wilfred; Nickoloff, Brian J.; Słomiński, Andrzej

doi:10.1290/1071-2690(2001)037<0234:hkefmm>2.0.co;2

Cited by 11 publications

(11 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Melanocytes from normal naevi were also negative for MC1R expression (Figure 2A (left panel)). It was previously described that human keratinocytes could specifically bind to a-MSH (Chakraborty et al, 1999;Curry et al, 2001). We confirmed the presence of MC1R in keratinocytes ( Figure 2B (K)), although the intensity of staining was weaker than that observed in the melanoma tissue from the same skin.…”

Section: Immunohistochemical Detection Of Mc1r On Paraffin-embedded Hsupporting

confidence: 85%

“…Of these, the melanocortin 1 receptor (MC1R) was originally described to be mainly located on melanoma and melanocytes (Varga et al, 1976;Tatro et al, 1990;Chhajlani, 1996;Suzuki et al, 1996;Xia et al, 1996). MC1R was, however, subsequently shown also to be expressed in various human tissues including human keratinocytes and monocytes (Chhajlani ans Wikberg, 1992;Rajora et al, 1996;Thörnwall et al, 1997;Chakraborty et al, 1999;Curry et al, 2001).…”

mentioning

confidence: 99%

“…Although there is evidence that MC1R has a broad distribution in various normal tissues including normal melanocytes, activated macrophages, and keratinocytes (Chhajlani, 1996;Rajora et al, 1996;Thörnwall et al, 1997;Chakraborty et al, 1999;Curry et al, 2001), this assessment is based mainly on qualitative or semi-quantitative methods. There is experimental and clinical evidence that immunotherapy based on administration of monoclonal antibodies or on specific tumour vaccines can also have an effect when based on non-mutated 'self-proteins' over-expressed in tumours, such as non-mutated p53, HER-2/neu, and gp100 (Ropke et al, 1996;Nagata et al, 1997;Rosenberg et al, 1998;Buchler et al, 2001;Slamon et al, 2001).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

Salazar‐Onfray

López

Lundqvist³

et al. 2002

Br J Cancer

106

111

View full text Add to dashboard Cite

The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT -PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I matched melanoma lines. The potential of targeting melanocortin 1 receptor in therapy and diagnosis will depend on a preferential expression of this receptor in the majority of primary and metastatic melanomas vs normal tissues. We tested a panel of melanomas, carcinomas and other cell lines for the presence of melanocortin 1 receptor, using two monoclonal antibodies. The receptor was detected in 83% of the tested melanoma cell lines but not in other carcinoma lines. Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas. Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1 receptor tissue distribution may be of relevance not only for melanoma immunology, but also for research on the pathogenicity of inflammatory conditions in the skin and neurologic tissues. It remains to be seen if the over-expression of melanocortin 1 receptor in melanomas is sufficiently high to allow a 'therapeutic window' to be exploited in cancer immunotherapy.

show abstract

Section: Immunohistochemical Detection Of Mc1r On Paraffin-embedded Hsupporting

confidence: 85%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

Salazar‐Onfray

López

Lundqvist³

et al. 2002

Br J Cancer

106

111

View full text Add to dashboard Cite

show abstract

“…Pro-inflammatory cytokines and UV radiation exposure were identified as physiological inducers of the skin POMC system, leading to the concept of a cutaneous analogon of the hypothalamic-pituitary-adrenal axis (19). Moreover, MC-1R has been demonstrated as being expressed by a variety of extra-pigmentary cell types of the skin, including dermal microvascular endothelial cells (20), epidermal keratinocytes (21), secretory epithelial cell types (22)(23)(24), and dermal fibroblasts (25).…”

mentioning

confidence: 99%

α-Melanocyte-stimulating Hormone Protects from Ultraviolet Radiation-induced Apoptosis and DNA Damage

Böhm

Wolff

Scholzen

et al. 2005

Journal of Biological Chemistry

215

155

View full text Add to dashboard Cite

Ultraviolet radiation is a well established epidemiologic risk factor for malignant melanoma. This observation has been linked to the relative resistance of normal melanocytes to ultraviolet B (UVB) radiation-induced apoptosis, which consequently leads to accumulation of UVB radiation-induced DNA lesions in melanocytes. Therefore, identification of physiologic factors regulating UVB radiation-induced apoptosis and DNA damage of melanocytes is of utmost biological importance. We show that the neuropeptide ␣-melanocyte-stimulating hormone (␣-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in vitro. The antiapoptotic activity of ␣-MSH is not mediated by filtering or by induction of melanin synthesis in melanocytes. ␣-MSH neither leads to changes in the cell cycle distribution nor induces alterations in the expression of the apoptosis-related proteins Bcl 2 , Bcl x , Bax, p53, CD95 (Fas/APO-1), and CD95L (FasL). In contrast, ␣-MSH markedly reduces the formation of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers, ultimately leading to reduced apoptosis. The reduction of UV radiation-induced DNA damage by ␣-MSH appears to be related to induction of nucleotide excision repair, because UV radiation-mediated apoptosis was not blocked by ␣-MSH in nucleotide excision repair-deficient fibroblasts. These data, for the first time, demonstrate regulation of UVB radiation-induced apoptosis of human melanocytes by a neuropeptide that is physiologically expressed within the epidermis. Apart from its ability to induce photoprotective melanin synthesis, ␣-MSH appears to exert the capacity to reduce UV radiation-induced DNA damage and, thus, may act as a potent protection factor against the harmful effects of UV radiation on the genomic stability of epidermal cells.Apoptosis of epidermal cells by ultraviolet B (UVB 1 ; 290 -320 nm) radiation is a well described phenomenon in vitro and in vivo and has been extensively studied in keratinocytes, the major target cells of solar UV radiation. It is considered a protective mechanism for minimizing the survival of cells with irreparable DNA damage (1), thereby preventing malignant transformation. The molecular pathways leading to UVB radiation-induced apoptosis include the formation of cyclobutane pyrimidine dimers (CPDs) and (6 -4) photoproducts (2, 3), the activation of death receptors including CD95 (Fas/APO-1) (2, 4), the release of death ligands, e.g. tumor necrosis factor-␣ (5, 6), and the formation of reactive oxygen species (7). These pathways are orchestrated by positive and negative factors that act within the epidermis in an autocrine and/or paracrine fashion. For example, hepatocyte growth factor/scatter factor produced by dermal fibroblasts inhibits UVB radiation-induced apoptosis of human keratinocytes via the phosphatidylinositol 3-kinase/AKT pathway (8). Insulin-like growth factor-1, which is expressed by melanocytes and fibroblasts (9), delays UVB radiation-induced apoptosis in human keratinocytes...

show abstract

“…Five different subtypes of MC receptors have been identified, designated MC-1 to MC-5. Melanocortin receptor-1 (MC-1), which is specific for ␣-MSH, is expressed on skin keratinocytes, dendritic cells, macrophages, endothelial cells, and epithelial cells (10,12).…”

mentioning

confidence: 99%

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

Raap

Brzoska²,

Sohl

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

α-Melanocyte-stimulating hormone (α-MSH) is a neuropeptide controlling melanogenesis in pigmentary cells. In addition, its potent immunomodulatory and immunosuppressive activity has been recently described in cutaneous inflammatory disorders. Whether α-MSH is also produced in the lung and might play a role in the pathogenesis of inflammatory lung conditions, including allergic bronchial asthma, is unknown. Production and functional role of α-MSH were investigated in a murine model of allergic airway inflammation. α-MSH production was detected in bronchoalveolar lavage fluids. Although aerosol challenges stimulate α-MSH production in nonsensitized mice, this rapid and marked stimulation was absent in allergic animals. Treatment of allergic mice with α-MSH resulted in suppression of airway inflammation. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to α-MSH treatment. This study provides evidence for a novel function of α-MSH linking neuroimmune functions in allergic airway inflammation.

show abstract

Human Keratinocytes Express Functional Α-MSH (Mc1-R) Receptors

Cited by 11 publications

References 13 publications

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

α-Melanocyte-stimulating Hormone Protects from Ultraviolet Radiation-induced Apoptosis and DNA Damage

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

Contact Info

Product

Resources

About