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Calcium influx blocked by SK&F 96365 modulates the LPS plus IFN-γ-induced inflammatory response in murine peritoneal macrophages.
MedLine Citation:
PMID:  22212354     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A rise in intracellular Ca(2+) ([Ca(2+)](i)) is crucial for the activation of macrophages, however, the mechanisms and consequences of this [Ca(2+)](i) increase remain unclear. This study investigated the role of calcium in mouse peritoneal macrophages stimulated with LPS plus IFN-γ by using the store-operated Ca(2+) channel (SOCC) blocker SK&F 96365. Our results showed that SK&F 96365 pretreatment significantly inhibited the elevation of [Ca(2+)](i) induced by ionomycin, thapsigargin, and LPS plus IFN-γ, respectively. Phagocytosis analyzing results showed that SK&F 96365 efficiently diminished the uptake of nonopsonized 1μM yellow-green beads or pHrodo™-labeled Escherichia coli bacteria both on the resting and LPS plus IFN-γ-stimulated macrophages. In addition, SK&F 96365 significantly inhibited the LPS plus IFN-γ-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-γ-induced inflammatory cytokines of IL-6, MCP-1, TNF, INF-γ, and IL-10. However, SK&F 96365 pretreatment did not inhibit but augment the production of LPS plus IFN-γ-induced IL-1β secretion. Furthermore, SK&F 96365 pretreatment inhibited the LPS plus IFN-γ-induced translocation of NF-κB to the nucleus, and induced a decrease in mitochondrial membrane potential (ΔΨm) in LPS plus IFN-γ-activated macrophages. This study provides insight into the role of calcium in the activation of peritoneal macrophages induced by LPS plus IFN-γ, and blocking the calcium influx by SK&F 96365 exhibited a domain inhibitory effect on the LPS plus IFN-γ-induced inflammatory response in macrophages.
Authors:
Yanxia Ye; Xiuyan Huang; Yaxing Zhang; Xinqiang Lai; Xiaoping Wu; Xiangfeng Zeng; Xiangao Tang; Yao-Ying Zeng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-30
Journal Detail:
Title:  International immunopharmacology     Volume:  -     ISSN:  1878-1705     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Affiliation:
Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, PR China.
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