Chymase inhibitor improves dermatitis in NC/Nga mice.
BACKGROUND
Mast cell chymase is thought to participate in allergic inflammation, but its precise role remains undetermined. Inbred NC/Nga mice develop skin lesions similar to atopic dermatitis (AD) when they grow up in a conventional environment. To elucidate the possible role of chymase in AD, we examined the effect of a chymase inhibitor on skin lesions of NC/Nga mice.


METHODS
NC/Nga mice were given the chymase inhibitor SUN-C8257 daily at 150 mg/kg/day with drinking water, and the severity of the dermatitis was evaluated on day 35 of the experiment. The role of chymase in dermatitis was further investigated in vitro and in vivo using recombinant mouse mast cell protease-4 (mMCP-4).


RESULTS
Administration of SUN-C8257 significantly reduced the clinical skin and histological score in NC/Nga mice. SUN-C8257 also inhibited the accumulation of inflammatory cells, such as eosinophils and mast cells, in the affected lesions in this model. mMCP-4 stimulated eosinophil migration in vitro, and intradermal injection of the enzyme resulted in a significant accumulation of inflammatory cells, including eosinophils, at the injection site. Thus amelioration of the skin lesions in NC/Nga mice by SUN-C8257 might be, at least in part, due to the suppression of cell infiltration in the lesions.


CONCLUSIONS
Mast cell chymase may contribute to the pathogenesis of AD, and SUN-C8257 will be beneficial to the treatment of the skin disorder.
Department of Tropical Medicine, Jikei University School of Medicine, Tokyo, Japan.
Naohiro
N
Watanabe
Yoshiaki
Y
Tomimori
Kayo
K
Saito
Kenju
K
Miura
Adumi
A
Wada
Masaoki
M
Tsudzuki
Yoshiaki
Y
Fukuda
D000818:Animals; D053818:Chymases; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053818:Chymases