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Lipopolysaccharide-Induced Expression of Microsomal Prostaglandin E Synthase-1 Mediates Late-Phase PGE2 Production in Bone Marrow Derived Macrophages

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Title: Lipopolysaccharide-Induced Expression of Microsomal Prostaglandin E Synthase-1 Mediates Late-Phase PGE2 Production in Bone Marrow Derived Macrophages
Author(s): Xiao, Lei; Ornatowska, Magdalena; Zhao, Guiqing; Cao, Hongmei; Yu, Rui; Deng, Jing; Li, Yongchao; Zhao, Qiong; Sadikot, Ruxana T.; Christman, John W.
Abstract: Cyclooxygenase (COX)-2 expression and release of prostaglandins (PGs) by macrophages are consistent features of lipopolysaccharide (LPS)-induced macrophage inflammation. The two major PGs, PGE(2) and PGD(2), are synthesized by the prostanoid isomerases, PGE synthases (PGES) and PGD synthases (PGDS), respectively. Since the expression profile and the individual role of these prostanoid isomerases-mediated inflammation in macrophages has not been defined, we examined the LPS-stimulated PGs production pattern and the expression profile of their synthases in the primary cultured mouse bone marrow derived macrophages (BMDM). Our data show that LPS induced both PGE(2) and PGD(2) production, which was evident by ∼8 hrs and remained at a similar ratio (∼1∶1) in the early phase (≤12 hrs) of LPS treatment. However, PGE(2) production continued increase further in the late phase (16-24 hrs); whereas the production of PGD(2) remained at a stable level from 12 to 24 hrs post-treatment. In response to LPS-treatment, the expression of both COX-2 and inducible nitric oxide synthase (iNOS) was detected within 2 to 4 hrs; whereas the increased expression of microsomal PGES (mPGES)-1 and a myeloid cell transcription factor PU.1 did not appear until later phase (≥12 hrs). In contrast, the expression of COX-1, hematopoietic-PGDS (H-PGDS), cytosolic-PGES (c-PGES), or mPGES-2 in BMDM was not affected by LPS treatment. Selective inhibition of mPGES-1 with either siRNA or isoform-selective inhibitor CAY10526, but not mPGES-2, c-PGES or PU.1, attenuated LPS-induced burst of PGE(2) production indicating that mPGES-1 mediates LPS-induced PGE(2) production in BMDM. Interestingly, selective inhibition of mPGES-1 was also associated with a decrease in LPS-induced iNOS expression. In summary, our data show that mPGES-1, but not mPGES-2 or c-PGES isomerase, mediates LPS-induced late-phase burst of PGE(2) generation, and regulates LPS-induced iNOS expression in BMDM.
Issue Date: 2012-11
Publisher: Public Library of Science
Citation Info: Xiao L, Ornatowska M, Zhao G, Cao H, Yu R, et al. (2012) Lipopolysaccharide-Induced Expression of Microsomal Prostaglandin E Synthase-1 Mediates Late-Phase PGE2 Production in Bone Marrow Derived Macrophages. PLoS ONE 7(11): e50244. doi:10.1371/journal.pone.0050244
Type: Article
Description: The original version is available through Public Library of Science at DOI: 10.1371/journal.pone.0050244. © 2012 Xiao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/10027/10678
ISSN: 1932-6203
Sponsor: Supported in part by National Institutes of Health (NIH, http://www.nih.gov/) grants 1R01 HL083218 (LX), 3R01 HL083218-01A2S1 (LX), and 5R01 HL075557 (JWC); Merit Review Grant 1I01BX000108 (JWC) from Jesse Brown VA Medical Center (http://www.va.gov/); Campus Research Board Grant S06-118 (LX) and Faculty Scholarship Support Grants (LX) from the University of Illinois at Chicago(http://www.uic.edu/uic/).
Date Available in INDIGO: 2013-11-26
 

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