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Induction of leukotriene B(4) and prostaglandin E(2) release from keratinocytes by protease-activated receptor-2-activating peptide in ICR mice.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2009 Oct; Vol. 9 (11), pp. 1332-6. Date of Electronic Publication: 2009 Aug 25. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Animals
Cetirizine pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Hydroxyurea analogs & derivatives
Hydroxyurea pharmacology
Indomethacin pharmacology
Injections, Intradermal
Keratinocytes metabolism
Male
Mice
Mice, Inbred ICR
Oligopeptides administration & dosage
Oligopeptides antagonists & inhibitors
Pruritus chemically induced
Pruritus etiology
Skin drug effects
Skin metabolism
Tacrolimus pharmacology
Dinoprostone metabolism
Keratinocytes drug effects
Leukotriene B4 metabolism
Oligopeptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 9
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19712758
- Full Text :
- https://doi.org/10.1016/j.intimp.2009.08.006