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Secretory Phospholipase A2-Potentiated Inducible Nitric Oxide Synthase Expression by Macrophages Requires NF-kB Activation1

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Author(s)
Yoon-Jeong LeeHyeun-Wook ChangSoo-Jung LeeSuk-Hwan BaekTaeg Kyu KwonJun-Hee LimJung-Hye KimKoing-Bo Kwun
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Journal of Immunology
Issued Date
2000
Volume
164
Issue
12
Abstract
The effect of secretory group II phospholipase A2 (sPLA2) on the expression of the inducible NO synthase (iNOS) and the production of NO by macrophages was investigated. sPLA2 by itself barely stimulated nitrite production and iNOS expression in Raw264.7 cells. However, in combination with LPS, the effects were synergistic. This potentiation was shown for sPLA2 enzymes from sPLA2-transfected stable cells or for purified sPLA2 from human synovial fluid. The effect of PLA2 on iNOS induction appears to be specific for the secretory type of PLA2. LPS-stimulated activation of iNOS was inhibited by the well-known selective inhibitors of sPLA2 such as 12-epi-scalaradial and ρ-bromophenacyl bromide. In contrast, the cytosolic PLA2-specific inhibitors methyl arachidonyl fluorophosphate and arachidonyltrifluoromethyl ketone did not affect LPS-induced nitrite production and iNOS expression. Moreover, when we transfected cDNA-encoding type II sPLA2, we observed that the sPLA2-transfected cells produced two times more nitrites than the empty vector or cytosolic PLA2-transfected cells. The sPLA2-potentiated iNOS expression was associated with the activation of NF-κB. We found that the NF-κB inhibitor pyrrolidinedithiocarbamate prevented nitrite production, iNOS induction, and mRNA accumulation by sPLA2 plus LPS in Raw264.7 cells. Furthermore, EMSA analysis of the activation of the NF-κB involved in iNOS induction demonstrated that pyrrolidinedithiocarbamate prevented the NF-κB binding by sPLA2 plus LPS. Our findings indicated that sPLA2, in the presence of LPS, is a potent activator of macrophages. It stimulates iNOS expression and nitrite production by a mechanism that requires the activation of NF-κB.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Yoon-Jeong Lee et al. (2000). Secretory Phospholipase A2-Potentiated Inducible Nitric Oxide Synthase Expression by Macrophages Requires NF-kB Activation1. Journal of Immunology, 164(12), 6359–6365. doi: 10.4049/jimmunol.164.12.6359
Type
Article
ISSN
0022-1767
DOI
10.4049/jimmunol.164.12.6359
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34055
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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