Increased alpha-melanocyte-stimulating hormone (alpha-MSH) levels and melanocortin receptors expression associated with pigmentation in an NC/Nga mouse model of atopic dermatitis.
Patients with a specific subtype of atopic dermatitis (AD) display particular patterns of pigmentation, such as ripple pattern pigmentation on the neck, pigmented macules on the lip and diffuse pigmentation. However, the mechanism underlying these patterns has not been determined. The purpose of our research is to investigate the factors influencing this type of pigmentation in AD. We observed that AD model mice (NC/Nga mice) displayed an increase in the number of 3, 4-dihydroxyphenylalanine (Dopa)-positive melanocytes in the epidermis and intestine (jejunum and colon) while in the inflammatory state. The plasma levels of alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocoticotropin (ACTH) also increased in NC/Nga mice with dermatitis. Furthermore, the expression of melanocortin receptor 5 and melanocortin receptor 1 (MC1R) increased in the skin, and melanocortin receptor 3 (MC3R) expression increased in the intestine. However, the changes in the Dopa-positive cells of conventional NC/Nga mice were not induced by treatment with either agouti (an MC1R antagonist) or agouti-related protein (an MC3R antagonist). These results indicate that the pigmentation of AD is related to increased levels of alpha-MSH, MC1R (in the skin) and MC3R (in the intestines).
Hiramoto
Keiichi
K
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, Osaka, Japan. hiramoto@msic.med.osaka-cu.ac.jp
Kobayashi
Hiromi
H
Ishii
Masamitsu
M
Sato
Eisuke
E
Inoue
Masayasu
M
D000324:Adrenocorticotropic Hormone / Q000097:blood; D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; D000818:Animals; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D051379:Mice; D010858:Pigmentation; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism*; D044104:Receptor, Melanocortin, Type 3 / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D000521:alpha-MSH / Q000097:blood*
D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; C470053:Mc3r protein, mouse; D044102:Receptor, Melanocortin, Type 1; D044104:Receptor, Melanocortin, Type 3; C515183:a protein, mouse; D000521:alpha-MSH; D004295:Dihydroxyphenylalanine; D000324:Adrenocorticotropic Hormone