Calcium influx blocked by SK&F 96365 modulates the LPS plus IFN-γ-induced inflammatory response in murine peritoneal macrophages

被引：40
作者：
Ye, Yanxia [1 ]
Huang, Xiuyan [1 ]
Zhang, Yaxing [1 ]
Lai, Xinqiang [2 ]
Wu, Xiaoping [1 ]
Zeng, Xiangfeng [1 ]
Tang, Xiangao [3 ]
Zeng, Yaoying [1 ]
机构：
[1] Jinan Univ, Inst Tissue Transplantat & Immunol, Guangzhou 510632, Guangdong, Peoples R China
[2] Jinan Univ, Expt Technol Ctr, Guangzhou 510632, Guangdong, Peoples R China
[3] Inst Regenerat Med, Natl Engn Lab Regenerat Implantable Med Devices, Guangzhou 510663, Guangdong, Peoples R China
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY | 2012年 / 12卷 / 02期
关键词：
LPS plus IFN-gamma; Macrophages; SK&F 96365; Calcium; Inflammatory response; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; FACTOR-KAPPA-B; INTRACELLULAR CA2+; ANTIMICROBIAL PEPTIDES; SIGNALING PATHWAYS; APOPTOTIC CELLS; PROTEIN-KINASES; ACTIVATION; RELEASE;
D O I：
10.1016/j.intimp.2011.12.011
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
A rise in intracellular Ca2+ ([Ca2+](i)) is crucial for the activation of macrophages, however, the mechanisms and consequences of this [Ca2+](i) increase remain unclear. This study investigated the role of calcium in mouse peritoneal macrophages stimulated with LPS plus IFN-gamma by using the store-operated Ca2+ channel (SOCC) blocker SK&F 96365. Our results showed that SK&F 96365 pretreatment significantly inhibited the elevation of [Ca2+](i) induced by ionomycin, thapsigargin, and LPS plus IFN-gamma, respectively. Phagocytosis analyzing results showed that SK&F 96365 efficiently diminished the uptake of nonopsonized 1 mu M yellow-green beads or pHrodo (TM)-labeled Escherichia coli bacteria both on the resting and LPS plus IFN-gamma-stimulated macrophages. In addition, SK&F 96365 significantly inhibited the LPS plus IFN-gamma-induced brisk uptake of NO and ROS. The CBA analyzing results showed that SK&F 96365 pretreatment efficiently inhibited the production of LPS plus IFN-gamma-induced inflammatory cytokines of IL-6, MCP-1, TNF, INF-gamma, and IL-10. However, SK&F 96365 pretreatment did not inhibit but augment the production of LPS plus IFN-gamma-induced IL-1 beta secretion. Furthermore, SK&F 96365 pretreatment inhibited the LPS plus IFN-gamma-induced translocation of NF-kappa B to the nucleus, and induced a decrease in mitochondrial membrane potential (Delta Psi m) in LPS plus IFN-gamma-activated macrophages. This study provides insight into the role of calcium in the activation of peritoneal macrophages induced by LPS plus IFN-gamma, and blocking the calcium influx by SK&F 96365 exhibited a domain inhibitory effect on the LPS plus IFN-gamma-induced inflammatory response in macrophages. (C) 2011 Elsevier B.V. All rights reserved.
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收藏
页码：384 / 393
页数：10
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