Oral chymase inhibitor SUN13834 ameliorates skin inflammation as well as pruritus in mouse model for atopic dermatitis.
Chymase is a chymotrypsin-like serine protease exclusively stored in secretory granules of mast cells and has been thought to participate in allergic diseases. It has already been shown that chymase inhibitor SUN13834 improves dermatitis in NC/Nga mice that spontaneously develop dermatitis resembling atopic dermatitis. In the present study, effect of chymase inhibitor SUN13834 on itch, the major feature of atopic dermatitis, was examined using a mouse dermatitis model induced by repeated topical application of 2,4-dinitrofluorobenzene (DNFB). Oral administration of SUN13834 once a day for 5 weeks inhibited not only skin swelling but accumulation of inflammatory cells including mast cells and eosinophils in the skin of the mice. In addition, SUN13834 also decreased significantly at 10 and 50 mg/kg the amount of scratching behavior induced by the DNFB challenge. This result indicates for the first time that mast cell chymase may be involved in itch induction. In conclusion, SUN13834 is thought to be useful as therapeutic agent for atopic dermatitis.
Terakawa
Maki
M
Asubio Pharma Co., Limited, Biomedical Research Laboratories, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
Fujieda
Yusuke
Y
Tomimori
Yoshiaki
Y
Muto
Tsuyoshi
T
Tanaka
Taisaku
T
Maruoka
Hiroshi
H
Nagahira
Kazuhiro
K
Ogata
Atsuto
A
Nakatsuka
Takashi
T
Fukuda
Yoshiaki
Y
D000284:Administration, Oral; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D053818:Chymases / Q000037:antagonists & inhibitors*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000503:physiopathology; D004139:Dinitrofluorobenzene; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology; D012867:Skin / Q000187:drug effects / Q000473:pathology
C538783:6-(5-chloro-2-methoxybenzyl)-4-alarkylaminocarbonyl-1,4-diazepane-2,5-dione; D001381:Azepines; D004791:Enzyme Inhibitors; D004139:Dinitrofluorobenzene; D053818:Chymases