PMID- 21470712 OWN - NLM STAT- MEDLINE DCOM- 20111228 LR - 20161125 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 216 IP - 9 DP - 2011 Sep TI - The anti-inflammatory effect of the SOCC blocker SK&F 96365 on mouse lymphocytes after stimulation by Con A or PMA/ionomycin. PG - 1044-53 LID - 10.1016/j.imbio.2011.03.001 [doi] AB - SK&F 96365, 51-(beta-[3-(p-methoxyphenyl)-propyloxy]-p-methoxyphenethyl)-1H-imidazole hydrochloride, has emerged as a useful pharmacological tool in the study of store-operated Ca(2)(+) 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 muM) 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 (DeltaPsim) 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. SK&F 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. CI - Copyright (c) 2011 Elsevier GmbH. All rights reserved. FAU - Ye, Yanxia AU - Ye Y AD - Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, PR China. FAU - Zhang, Yaxing AU - Zhang Y FAU - Lu, Xiaoyu AU - Lu X FAU - Huang, Xiuyan AU - Huang X FAU - Zeng, Xiangfeng AU - Zeng X FAU - Lai, Xinqiang AU - Lai X FAU - Zeng, Yaoying AU - Zeng Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110312 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (5-(6)-carboxyfluorescein diacetate succinimidyl ester) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antigens, CD) RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium Channels) RN - 0 (Cytokines) RN - 0 (Fluoresceins) RN - 0 (Fluorescent Dyes) RN - 0 (Imidazoles) RN - 0 (Succinimides) RN - 11028-71-0 (Concanavalin A) RN - 56092-81-0 (Ionomycin) RN - 67526-95-8 (Thapsigargin) RN - I61V87164A (1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Anti-Inflammatory Agents/immunology/pharmacology MH - Antigens, CD/biosynthesis/immunology MH - Calcium/immunology/*metabolism MH - Calcium Channel Blockers/immunology/pharmacology MH - Calcium Channels/immunology/*metabolism MH - Cell Cycle/*drug effects/immunology MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Concanavalin A/immunology/pharmacology MH - Cytokines/biosynthesis/immunology MH - Dose-Response Relationship, Drug MH - Female MH - Fluoresceins/analysis MH - Fluorescent Dyes/analysis MH - Imidazoles/immunology/*pharmacology MH - Inflammation/drug therapy/*immunology/pathology MH - Ionomycin/immunology/pharmacology MH - Lymphocyte Activation/drug effects MH - Lymphocyte Count MH - Membrane Potential, Mitochondrial/drug effects/immunology MH - Mice MH - Mice, Inbred BALB C MH - Mitochondria/drug effects/immunology MH - Signal Transduction/*drug effects/immunology MH - Succinimides/analysis MH - T-Lymphocytes/*drug effects/immunology MH - Tetradecanoylphorbol Acetate/immunology/pharmacology MH - Thapsigargin/immunology/pharmacology EDAT- 2011/04/08 06:00 MHDA- 2011/12/29 06:00 CRDT- 2011/04/08 06:00 PHST- 2010/12/12 00:00 [received] PHST- 2011/03/03 00:00 [revised] PHST- 2011/03/05 00:00 [accepted] PHST- 2011/04/08 06:00 [entrez] PHST- 2011/04/08 06:00 [pubmed] PHST- 2011/12/29 06:00 [medline] AID - S0171-2985(11)00048-9 [pii] AID - 10.1016/j.imbio.2011.03.001 [doi] PST - ppublish SO - Immunobiology. 2011 Sep;216(9):1044-53. doi: 10.1016/j.imbio.2011.03.001. Epub 2011 Mar 12.