The anti-inflammatory effect of the SOCC blocker SK&F 96365 on mouse lymphocytes after stimulation by Con A or PMA/ionomycin
文献类型： 外文期刊
作者： Ye, Yanxia 1 ; Zhang, Yaxing 1 ; Lu, Xiaoyu 1 ; Huang, Xiuyan 1 ; Zeng, Xiangfeng 1 ; Lai, Xinqiang 3 ; Zeng, Yaoying 1 ;
作者机构： 1.Jinan Univ, Inst Tissue Transplantat & Immunol, Guangzhou 510632, Guangdong, Peoples R China
2.Guangdong Acad Agr Sci, Guangzhou 510640, Guangdong, Peoples R China
3.Jinan Univ, Expt Technol Ctr, Guangzhou 510632, Guangdong, Peoples R China
关键词： SK&F 96365;Lymphocytes;Con A;PMA/ionomycin;Proliferation;MPT;Anti-inflammatory
期刊名称：IMMUNOBIOLOGY （ 影响因子：3.144； 五年影响因子：3.18 ）
ISSN： 0171-2985
年卷期： 2011 年 216 卷 9 期
页码：
收录情况： SCI
摘要： SK&F 96365, 51-(beta-(3-(p-methoxyphenyl)-propyloxyl-p-methoxyPhenethyl)-1H-imidazole hydrochloride, has emerged as a useful pharmacological tool in the study of store-operated Ca2(+) entry (SOCE). But the precise molecular mechanism and effect of SK&F 96365 on mouse lymphocytes are still not well determined. This study investigated the pharmacological profile of SK&F 96365 on mouse lymphocytes stimulated by mitogen concanavalin A (Con A) or by a combination of a protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA) and a calcium ionophore, ionomycin in vitro. Our results showed that SK&F 96365 pre-treatment diminished the cytosolic calcium rise on lymphocytes induced by ionomycin, PMA/ionomycin, and thapsigargin (TG), respectively. CFDA-SE staining results showed that SK&F 96365 (5-20 mu M) inhibited both Con A- and PMA/ionomycin-induced lymphocytes proliferation in a time- and dose-dependent manner. Upon the same stimulation, SK&F 96365 inhibited the expression of CD69 and CD25 on CD3(+) T lymphocytes in a dose-dependent manner. The cell cycle analyzing results showed that SK&F 96365 caused a G0/G1 phase cell cycle arrest on both Con A- and PMA/ionomycin-activated lymphocytes in a dose-dependent manner. In addition, SK&F 96365 induced a decrease in mitochondrial membrane potential (Delta Psi m) and promoted mitochondrial permeability transition (MPT) in both Con A- and PMA/ionomycin-activated lymphocytes. Furthermore, SK&F 96365 significantly inhibited the production of proinflammatory cytokines (interferon (IFN)-gamma and tumor necrosis factor (TNF)), and the anti-inflammatory cytokine (IL-10) on both Con A- and PMA/ionomycin-activated lymphocytes. SK82F 96365 did not induce a statistically significant increase in levels of proinflammatory IL-6 and monocyte chemoattractant protein-1 (MCP-1) but of IL-12p70 upon the stimulation of Con A, whereas these three cytokines were markedly inhibited by it upon the stimulation of PMA/ionomycin. This finding revealed that SK&F 96365 exhibited an anti-inflammatory effect on mouse lymphocytes both upon the stimulation of Con A and PMA/ionomycin, and the precise mechanism of SK&F 96365 inhibiting Con A-activated lymphocytes proliferation is different from PMA/ionomycin. (C) 2011 Elsevier GmbH. All rights reserved.
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