Induction of leukotriene B(4) and prostaglandin E(2) release from keratinocytes by protease-activated receptor-2-activating peptide in ICR mice.
Protease-activated receptor-2 (PAR2) has been shown to play a key role in the pathophysiology of itch. However, the precise mechanism of PAR2-mediated itch remains largely unknown. In the present study, we investigated the effects of several agents on the scratching behavior induced by PAR2-activating peptide (SLIGRL-NH2). Pretreatment of experimental animals with tacrolimus or the 5-lipoxygenase inhibitor zileuton significantly reduced SLIGRL-NH2-induced scratching behavior, whereas histamine H(1) receptor antagonist cetirizine or the cyclooxygenase inhibitor indomethacin had little effect. Furthermore, intradermal injection of SLIGRL-NH2 increased cutaneous levels of LTB(4) and PGE(2). In vitro, SLIGRL-NH2 treatment enhanced LTB(4) and PGE(2) release from primary keratinocytes in a concentration-dependent manner. Preincubation of keratinocytes with zileuton resulted in a significant decrease of LTB(4) release and treatment of indomethacin led to a significant decrease of PGE(2) in response to SLIGRL-NH2 stimulation. In addition, SLIGRL-NH2-induced secretion of LTB(4) and PGE(2) was significantly inhibited by tacrolimus, whereas cetirizine had no effect. These results indicate that SLIGRL-NH2 stimulates LTB(4) and PGE(2) release from mouse keratinocytes and that enhancement of LTB(4) and PGE(2) secretion contributes to SLIGRL-NH2-induced scratching behavior in ICR mice.
Zhu
Yu
Y
Department of Pharmacy, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China.
Wang
Xiao Rong
XR
Peng
Cheng
C
Xu
Jian Guo
JG
Liu
Yan Xia
YX
Wu
Liang
L
Zhu
Quan Gang
QG
Liu
Ji Yong
JY
Li
Feng Qian
FQ
Pan
Yong Hua
YH
You
Ben Ming
BM
Hu
Jin Hong
JH
D000818:Animals; D017332:Cetirizine / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007271:Injections, Intradermal; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011537:Pruritus / Q000139:chemically induced / Q000209:etiology; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology
D009842:Oligopeptides; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D007975:Leukotriene B4; D015232:Dinoprostone; C063449:zileuton; D016559:Tacrolimus; D006918:Hydroxyurea; D007213:Indomethacin; D017332:Cetirizine