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薬理と治療
- Authors: Takeshi Kogahara1, Kazuhito Asano2, Kenichi Kanai1, Ayako Furuya1, Naotoshi Imajima1, Hisashi Nishisako2, Tadashi Hisamitsu1, Harumi Suzaki2
Abstract
Objective The purpose of the present study was to examine the influence of epinastine hydrochloride(EP), a second generation H1 receptor antagonist, on the function of monocytederived dendritic cells(MoDCs)in vitro. Methods MoDCs were differentiated from peripheral blood monocytes from healthy subjects with GM−CSF and IL−4. After LPS stimulation of MoDCs in the presence or absence of either EP or chlorpheniramine(CH), cell surface molecules(CD40, CD80 and CD86), as well as concentrations of TNF−α, IL−6, IL−12p35, IL−12p70 and IL−10 in culture supernatants, were examined by flow cytometer and ELISA, respectively. We also examined the influence of EP on the ability of MoDCs to stimulate allogeneic CD4+ T cells by examining T cell proliferation and cytokine(IL−4 and IFN−γ)secretion. Results EP significantly inhibited the up−regulation of cell surface marker, CD40, CD80 and CD86, expression on MoDCs induced by LPS stimulation. EP also suppressed the secretion of TNF−α, IL−6, IL−12p35, and IL−12p70, which were up−regulated by LPS stimulation, however, the secretion of IL−10 was not affected. Treatment of MoDCs with EP down−regulated both the allostimulatory function and the capacity to stimulate CD4+ T cells to secrete IL−4 and IFN−γ. Moreover, EP inhibits the down−regulation of fluorescein isothiocyanate− dextran uptake during DC maturation. In contrast, CH had little or no effect on DC maturation. Conclusion EP interferes the function of MoDCs and results in favorable modification of the allergic disease state.(Jpn Pharmacol Ther 2008;36:1105−18)KEY WORDS Dendritic cells, Co−stimulatory molecule, IL−10, IL−12, Epinastine hydrochloride
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