TY - JOUR
T1 - Cathepsin e induces itch-related response through the production of endothelin-1 in mice
AU - Andoh, Tsugunobu
AU - Yoshida, Tetsuro
AU - Lee, Jung Bum
AU - Kuraishi, Yasushi
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Young Scientists (B) # 22790063 and for Scientific Research (B) # 23390153 from the Ministry of Education, Culture, Sports, Science and Technology, Japan and by Grants for Health Science from the Health, Labor and Welfare Ministry, Japan .
PY - 2012/7/5
Y1 - 2012/7/5
N2 - This study investigated the pruritogenic potency of cathepsin E, an aspartic protease, and its mechanisms in mice. An intradermal injection of cathepsin E to the rostral back elicited scratching, an itch-associated response, of the injection site. This action was inhibited by the aspartic protease inhibitor pepstatin A, the endothelin ET A receptor antagonist BQ-123, and the opioid receptor antagonists naltrexone and naloxone, but not by the H 1 histamine receptor antagonist terfenadine, the proteinase-activated receptor-2 antagonist FSLLRY-NH 2, or mast cell deficiency. Pepstatin A inhibited scratching induced by intradermal injection of the mast-cell degranulator compound 48/80, but not by tryptase, a mast-cell mediator. An intradermal injection of cathepsin E increased endothelin-1 levels in the skin at the injection site. Preproendothelin-1 mRNA was present in primary cultures of keratinocytes, and immunohistochemistry using an antibody recognizing endothelin-1 and big-endothelin-1 revealed immunoreactivity in the epidermis, especially in the prickle and granular cell layers, but not in the basal cell layer. These results suggest that cathepsin E is an endogenous itch inducer, and that its action is mediated at least in part by the production of endothelin-1 in the epidermis.
AB - This study investigated the pruritogenic potency of cathepsin E, an aspartic protease, and its mechanisms in mice. An intradermal injection of cathepsin E to the rostral back elicited scratching, an itch-associated response, of the injection site. This action was inhibited by the aspartic protease inhibitor pepstatin A, the endothelin ET A receptor antagonist BQ-123, and the opioid receptor antagonists naltrexone and naloxone, but not by the H 1 histamine receptor antagonist terfenadine, the proteinase-activated receptor-2 antagonist FSLLRY-NH 2, or mast cell deficiency. Pepstatin A inhibited scratching induced by intradermal injection of the mast-cell degranulator compound 48/80, but not by tryptase, a mast-cell mediator. An intradermal injection of cathepsin E increased endothelin-1 levels in the skin at the injection site. Preproendothelin-1 mRNA was present in primary cultures of keratinocytes, and immunohistochemistry using an antibody recognizing endothelin-1 and big-endothelin-1 revealed immunoreactivity in the epidermis, especially in the prickle and granular cell layers, but not in the basal cell layer. These results suggest that cathepsin E is an endogenous itch inducer, and that its action is mediated at least in part by the production of endothelin-1 in the epidermis.
KW - Cathepsin E
KW - Endothelin-1
KW - Itch
KW - Keratinocyte
KW - Mast cell
KW - Scratching
UR - http://www.scopus.com/inward/record.url?scp=84861634949&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2012.04.024
DO - 10.1016/j.ejphar.2012.04.024
M3 - 学術論文
C2 - 22546226
AN - SCOPUS:84861634949
SN - 0014-2999
VL - 686
SP - 16
EP - 21
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -