1. Induction of leukotriene B4 and prostaglandin E2 release from keratinocytes by protease-activated receptor-2-activating peptide in ICR mice
- Author
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Zhu, Yu, Wang, Xiao Rong, Peng, Cheng, Xu, Jian Guo, Liu, Yan Xia, Wu, Liang, Zhu, Quan Gang, Liu, Ji Yong, Li, Feng Qian, Pan, Yong Hua, You, Ben Ming, and Hu, Jin Hong
- Subjects
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LEUKOTRIENES , *PROSTAGLANDINS E , *KERATINOCYTES , *PROTEOLYTIC enzymes , *PEPTIDES , *LABORATORY mice , *PATHOLOGICAL physiology , *ITCHING - Abstract
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 H1 receptor antagonist cetirizine or the cyclooxygenase inhibitor indomethacin had little effect. Furthermore, intradermal injection of SLIGRL-NH2 increased cutaneous levels of LTB4 and PGE2. In vitro, SLIGRL-NH2 treatment enhanced LTB4 and PGE2 release from primary keratinocytes in a concentration-dependent manner. Preincubation of keratinocytes with zileuton resulted in a significant decrease of LTB4 release and treatment of indomethacin led to a significant decrease of PGE2 in response to SLIGRL-NH2 stimulation. In addition, SLIGRL-NH2-induced secretion of LTB4 and PGE2 was significantly inhibited by tacrolimus, whereas cetirizine had no effect. These results indicate that SLIGRL-NH2 stimulates LTB4 and PGE2 release from mouse keratinocytes and that enhancement of LTB4 and PGE2 secretion contributes to SLIGRL-NH2-induced scratching behavior in ICR mice. [Copyright &y& Elsevier]
- Published
- 2009
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