Background: The effect of epinastin hydrochloride on leukocyte migration is unclear. Objectives: The objective of the current study is to elucidate the effect of epinastin hydrochloride on the function of cell adhesion molecules that regulate the capture/rolling process of leukocyte migration during contact hypersensitivity (CHS). Methods: The effect of epinastin hydrochloride on CHS was investigated in mice lacking either P-selectin, E-selectin, or P-selectin glycoprotein-1 (PSGL-1), a ligand for both P-and E-selectins. Mice were sensitized by application of the immunogen onto back skin and ears were challenged 5 days later. Twelve hours before challenge, mice were treated with epinastin hydrochloride orally. Results: At 48 hours after hapten challenge, oral treatment with epinastin hydrochloride significantly suppressed ear swelling and cutaneous inflammatory cell migration in P-selectin-deficient mice, but not in the wild type mice, E-selectin-deficient mice, or PSGL-1-deficient mice. Given that E-selectin has overlapping function with P-selectin during CHS, the finding that epinastin hydrochloride inhibited CHS response in P-selectin-deficient mice suggests that epinastin hydrochloride suppressed CHS response by inhibiting E-selection function. Conclusions: Epinastin hydrochloride exhibits anti-inflammatory function by regulating the function of E-selectin.
|ジャーナル||Japanese Pharmacology and Therapeutics|
|出版ステータス||Published - 2008|
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