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PMID: 21190819 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genetic deletion of mPGES-1 abolishes PGE2 production in murine dendritic cells and alters the cytokine profile, but does not affect maturation or migration.

Prostaglandins, leukotrienes, and essential fatty acids ·Vol. 84 ·No. 3-4 ·2011-00-00 ·Pages 113-21

Monrad SU, Kojima F, Kapoor M, Kuan EL, Sarkar S, Randolph GJ, Crofford LJ

Abstract

We undertook this study to determine the role of Microsomal PGE Synthase-1 (mPGES-1), and mPGES-1-generated Prostaglandin (PG) E2 on Dendritic Cell (DC) phenotype and function. Using mPGES-1 KnockOut (KO) mice, we generated bone marrow derived DCs and determined their eicosanoid production profile, cell surface marker expression, and cytokine production. We also assessed DC migratory and functional capacity in vivo. Compared to wild-type, mPGES-1 deficient DCs exhibited a markedly attenuated increase in PGE2 production upon LPS stimulation, and displayed preferential shunting towards PGD2 production. mPGES-1 KO DCs did not display deficiencies in maturation, migration or ability to sensitize T cells. However, mPGES-1 deficient DCs generated reduced amounts of the Th1 cytokine IL-12, which may in part be due to increased PGD2 rather than decreased PGE2. These findings provide useful information on the effects of inducible PGE2 on the innate immune system, and have important implications regarding potential consequences of pharmacologic mPGES-1 inhibition.

MeSH Terms
Animals Cell Movement/genetics Cricetinae Cytokines/metabolism Dendritic Cells/metabolism Dinoprostone/biosynthesis Gene Deletion Interleukin-12/metabolism Intramolecular Oxidoreductases/genetics,metabolism Lipopolysaccharides/pharmacology Mice Mice, Knockout Prostaglandin-E Synthases Rats
Chemicals
Cytokines Lipopolysaccharides Interleukin-12 Intramolecular Oxidoreductases Prostaglandin-E Synthases Ptges protein, mouse Dinoprostone
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Monrad S U
Department of Internal Medicine, University of Michigan, Ann Arbor, 48109, USA.
Kojima F
Kapoor M
Kuan E L
Sarkar S
Randolph G J
Crofford L J
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Article Info
Journal
Prostaglandins, leukotrienes, and essential fatty acids
Abbr.
Prostaglandins Leukot Essent Fatty Acids
ISSN
1532-2823
DOI
10.1016/j.plefa.2010.10.003
Published
2011-00-00
Epub
2010-00-28
Pages
113-21
Language
English
Region
Scotland
NLM ID
8802730
PMCID
PMC3072052
Subset
IM
Grants
NIAMS NIH HHS · AR049010 · United States
NIAID NIH HHS · R01 AI061741 · United States
NIAID NIH HHS · R01 AI049653 · United States
NIAID NIH HHS · AI49653 · United States
NIAMS NIH HHS · R01 AR049010 · United States
NIAMS NIH HHS · R01 AR049010-06A1 · United States
External Links
PubMed source DOI: 10.1016/j.plefa.2010.10.003 PMC Full Text View journal details
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