TY - JOUR
T1 - Genetic deletion of mPGES-1 abolishes PGE2 production in murine dendritic cells and alters the cytokine profile, but does not affect maturation or migration
AU - Monrad, S. U.
AU - Kojima, F.
AU - Kapoor, M.
AU - Kuan, E. L.
AU - Sarkar, S.
AU - Randolph, G. J.
AU - Crofford, L. J.
N1 - Funding Information:
This work was supported in part by an American College of Rheumatology Research and Education Foundation Physician-Scientist Development Award (S.U.M.), a National Institutes of Health grants AI49653 (G.J.R.), an Established Investigator Award from the American Heart Association (G.J.R.) and a National Institutes of Health grants AR049010 (L.J.C.).
Funding Information:
Dr. Crofford has had grant funding from Pfizer. She is not a consultant and not a participant in any Speaker's Bureau and does not own stock.
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - Cytokine
KW - Dendritic cells
KW - Maturation
KW - Microsomal prostaglandin E synthase
KW - Migration
UR - http://www.scopus.com/inward/record.url?scp=79151469472&partnerID=8YFLogxK
U2 - 10.1016/j.plefa.2010.10.003
DO - 10.1016/j.plefa.2010.10.003
M3 - Article
C2 - 21190819
AN - SCOPUS:79151469472
SN - 0952-3278
VL - 84
SP - 113
EP - 121
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
IS - 3-4
ER -