Genetic Deletion of MPGES-1 Abolishes PGE2 Production in Murine Dendritic Cells and Alters the Cytokine Profile, but Does Not Affect Maturation or Migration

Overview

Journal Prostaglandins Leukot Essent Fatty Acids

Specialty Endocrinology

Date 2010 Dec 31

PMID 21190819

Citations 21

Authors

S U Monrad

F Kojima

M Kapoor

E L Kuan

S Sarkar

G J Randolph

L J Crofford

Affiliations

Soon will be listed here.

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.

Citing Articles

Microsomal Prostaglandin E Synthase-1 Controls Colonic Prostaglandin E Production and Exerts a Protective Effect on Colitis Induced by Trinitrobenzene Sulfonic Acid in Mice.

Kojima F, Hioki Y, Sekiya H, Kashiwagi H, Iizuka Y, Eto K Int J Mol Sci. 2024; 25(22).

PMID: 39596393 PMC: 11594388. DOI: 10.3390/ijms252212326.

Epithelial Cell-specific Deletion of Microsomal Prostaglandin E Synthase-1 Does Not Influence Colon Tumor Development in Mice.

Nakanishi M, Rosenberg D J Cancer Prev. 2022; 26(4):304-308.

PMID: 35047457 PMC: 8749314. DOI: 10.15430/JCP.2021.26.4.304.

Facilitation of colonic T cell immune responses is associated with an exacerbation of dextran sodium sulfate-induced colitis in mice lacking microsomal prostaglandin E synthase-1.

Kojima F, Sekiya H, Hioki Y, Kashiwagi H, Kubo M, Nakamura M Inflamm Regen. 2022; 42(1):1.

PMID: 34983695 PMC: 8725565. DOI: 10.1186/s41232-021-00188-1.

Upregulation of Cytokines and Differentiation of Th17 and Treg by Dendritic Cells: Central Role of Prostaglandin E2 Induced by .

Liu H, Xiong X, Zhai W, Zhu T, Zhu X, Zhu Y Microorganisms. 2020; 8(2).

PMID: 32023904 PMC: 7074778. DOI: 10.3390/microorganisms8020195.

mPGES-1-Mediated Production of PGE and EP4 Receptor Sensing Regulate T Cell Colonic Inflammation.

Maseda D, Banerjee A, Johnson E, Washington M, Kim H, Lau K Front Immunol. 2019; 9:2954.

PMID: 30619314 PMC: 6302013. DOI: 10.3389/fimmu.2018.02954.

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