Time course changes of scratching counts, dermatitis symptoms, and levels of cutaneous prostaglandins in NC/Nga mice.
NC/Nga (NC) mice are known to develop dermatitis resembling atopic dermatitis (AD) in conventional (Conv) conditions, but not in specific pathogen-free (SPF) conditions. We reported that the ability of skin prostaglandin D(2) (PGD(2)) production, which might be the endogenous inhibitor of itching, was attenuated in skin-lesioned Conv-NC mice. We examined the age-related change in scratching, dermatitis symptoms, and skin PGs of SPF- and Conv-NC mice. In Conv-NC, PGD(2) increased at 7 weeks, at which scratching counts increased, but dermatitis did not develop. PGE(2), PGI(2) and PGF(2alpha) increased at 10 and 13 weeks, at which dermatitis developed. The ability to produce skin PGs was examined by measuring PGs after application of arachidonic acid or after mechanical scratching using a wire brush. In Conv-NC, PGD(2) production at 13 weeks was lower than at 7 weeks. In Conv-NC, hematopoietic PGD synthase (hPGDS) expression in the skin at 13 weeks was lower than at 7 weeks by Western blotting and immunohistochemical analysis. The increase of skin PGD(2) level in the early phase of the development of dermatitis is due to the stress of extensive scratching, but did not increase in spite of the stress of extensive scratching in the late phase, due to decreasing capacity of PGD(2) production attributable to decreasing hPGDS expression in Conv-NC mice. These results suggest that a decreased ability to produce skin PGD(2) production could enhance scratching and aggravate dermatitis in Conv-NC mice.
Sugimoto
Masanori
M
Department of Pharmacology, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, Saitama, Japan. masanori.sugimoto@po.rd.taisho.co.jp
Arai
Iwao
I
Futaki
Nobuko
N
Hashimoto
Yuki
Y
Sakurai
Takanobu
T
Honma
Yusuke
Y
Nakaike
Shiro
S
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D015153:Blotting, Western; D003872:Dermatitis / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D054834:Lipocalins; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D015230:Prostaglandin D2 / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011537:Pruritus / Q000378:metabolism*; D012720:Severity of Illness Index; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D054834:Lipocalins; D011453:Prostaglandins; D016718:Arachidonic Acid; D015237:Dinoprost; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015232:Dinoprostone; D015230:Prostaglandin D2