TY - JOUR
T1 - Involvement of tryptase and proteinase-activated receptor-2 in spontaneous itch-associated response in mice with atopy-like dermatitis
AU - Tsujii, Kenichiro
AU - Andoh, Tsugunobu
AU - Ui, Haruna
AU - Lee, Jung Bum
AU - Kuraishi, Yasushi
PY - 2009
Y1 - 2009
N2 - This study investigated the involvement of tryptase and proteinase-activated receptor (PAR) subtypes in spontaneous scratching, an itch-associated behavior, in NC mice. This strain of mice showed chronic atopy-like dermatitis and severe spontaneous scratching, when kept a long time in a conventional environment. The trypsin-like serine proteinase inhibitor nafamostat mesilate (1-10mg/kg) dose-dependently inhibited spontaneous scratching in mice with dermatitis. The activity of tryptase was increased in the lesional skin, which was inhibited by nafamostat at a dose inhibiting spontaneous scratching. Enzyme histochemistry revealed the marked increase of toluidine blue-stained cells, probably mast cells, with tryptase activity in the dermis of the lesional skin. Intravenous injection of anti-PAR2 antibody suppressed spontaneous scratching of mice with dermatitis. Intradermal injection of the PAR2-activating peptide SLI- GRL-NH2, but not PARi, 3, 4-activating peptides, elicited scratching at doses of 10-100 nmol/site in healthy mice. PAR2-immunoreactivity was observed in the epidermal keratinocytes in healthy and dermatitis mice. These results suggest that PAR2 and serine proteinase(s), mainly tryptase, are involved in the itch of chronic dermatitis.
AB - This study investigated the involvement of tryptase and proteinase-activated receptor (PAR) subtypes in spontaneous scratching, an itch-associated behavior, in NC mice. This strain of mice showed chronic atopy-like dermatitis and severe spontaneous scratching, when kept a long time in a conventional environment. The trypsin-like serine proteinase inhibitor nafamostat mesilate (1-10mg/kg) dose-dependently inhibited spontaneous scratching in mice with dermatitis. The activity of tryptase was increased in the lesional skin, which was inhibited by nafamostat at a dose inhibiting spontaneous scratching. Enzyme histochemistry revealed the marked increase of toluidine blue-stained cells, probably mast cells, with tryptase activity in the dermis of the lesional skin. Intravenous injection of anti-PAR2 antibody suppressed spontaneous scratching of mice with dermatitis. Intradermal injection of the PAR2-activating peptide SLI- GRL-NH2, but not PARi, 3, 4-activating peptides, elicited scratching at doses of 10-100 nmol/site in healthy mice. PAR2-immunoreactivity was observed in the epidermal keratinocytes in healthy and dermatitis mice. These results suggest that PAR2 and serine proteinase(s), mainly tryptase, are involved in the itch of chronic dermatitis.
KW - Atopic dermatitis
KW - Itch
KW - Proteinase-activated receptor
KW - Scratching
KW - Tryptase
UR - http://www.scopus.com/inward/record.url?scp=67249103872&partnerID=8YFLogxK
U2 - 10.1254/jphs.08332FP
DO - 10.1254/jphs.08332FP
M3 - 学術論文
C2 - 19270428
AN - SCOPUS:67249103872
SN - 1347-8613
VL - 109
SP - 388
EP - 395
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
IS - 3
ER -