HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Petrova, T. V. Articles by Van Eldik, L. J. Search for Related Content PubMed PubMed Citation Articles by Petrova, T. V. Articles by Van Eldik, L. J. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 40, 28823-28827, October 1, 1999

Selective Modulation of BV-2 Microglial Activation by Prostaglandin E₂
DIFFERENTIAL EFFECTS ON ENDOTOXIN-STIMULATED CYTOKINE INDUCTION

Tatiana V. Petrova, Keith T. Akama, and Linda J. Van Eldik^§

From the  Department of Cell and Molecular Biology and ^§ Northwestern Drug Discovery Program, Northwestern University Medical School, Chicago, Illinois 60611

The influence of prostaglandins on glial functions and, more specifically, on glial activation is not well understood. We report here that prostaglandin E₂ (PGE₂), one of the major prostaglandins produced in the brain, acts as a potent and selective inhibitor of tumor necrosis factor  (TNF-) production in lipopolysaccharide-stimulated primary microglia and the microglial cell line BV-2. The IC₅₀ for this effect is 1 nM, and 100 nM PGE₂ suppresses TNF- production by >95%. More detailed studies of BV-2 cells show that PGE₂ also prevents the secretion of interleukin (IL)-6 but does not significantly modify lipopolysaccharide-stimulated expression of cyclooxygenase-2, pro-IL-1, or inducible nitric oxide synthase. PGE₂ appears to act primarily at the level of translation or protein stability, because TNF- and IL-6 mRNA levels were only modestly decreased at high PGE₂ concentrations; concomitantly with this inhibition, PGE₂ up-regulated the levels of IL-1 mRNA. The effects of PGE₂ could be largely mimicked by 8-bromo-cAMP, suggesting that, as in other cell types, PGE₂ action is mediated at least in part by a rise in intracellular cyclic AMP. However, the protein kinase A inhibitor H89 only partially reversed the inhibition of TNF- production by PGE₂, implying that the PGE₂ effect in BV-2 cells is mediated through both protein kinase A-dependent and -independent pathways.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Jang, K. W. Kelley, and R. W. Johnson Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1 PNAS, May 27, 2008; 105(21): 7534 - 7539. [Abstract] [Full Text] [PDF]

				H. Qin, K. L. Roberts, S. A. Niyongere, Y. Cong, C. O. Elson, and E. N. Benveniste Molecular Mechanism of Lipopolysaccharide-Induced SOCS-3 Gene Expression in Macrophages and Microglia J. Immunol., November 1, 2007; 179(9): 5966 - 5976. [Abstract] [Full Text] [PDF]

				I. Mohri, M. Taniike, H. Taniguchi, T. Kanekiyo, K. Aritake, T. Inui, N. Fukumoto, N. Eguchi, A. Kushi, H. Sasai, et al. Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher. J. Neurosci., April 19, 2006; 26(16): 4383 - 4393. [Abstract] [Full Text] [PDF]

				F.-S. Shie, R. M. Breyer, and T. J. Montine Microglia Lacking E Prostanoid Receptor Subtype 2 Have Enhanced A{beta} Phagocytosis yet Lack A{beta}-Activated Neurotoxicity Am. J. Pathol., April 1, 2005; 166(4): 1163 - 1172. [Abstract] [Full Text] [PDF]

				S. Giri, R. Rattan, A. K. Singh, and I. Singh The 15-Deoxy-{delta}12,14-Prostaglandin J2 Inhibits the Inflammatory Response in Primary Rat Astrocytes via Down-Regulating Multiple Steps in Phosphatidylinositol 3-Kinase-Akt-NF-{kappa}B-p300 Pathway Independent of Peroxisome Proliferator-Activated Receptor {gamma} J. Immunol., October 15, 2004; 173(8): 5196 - 5208. [Abstract] [Full Text] [PDF]

				B. Zingarelli, M. Sheehan, P. W. Hake, M. O'Connor, A. Denenberg, and J. A. Cook Peroxisome Proliferator Activator Receptor-{gamma} Ligands, 15-Deoxy-{Delta}12,14-Prostaglandin J2 and Ciglitazone, Reduce Systemic Inflammation in Polymicrobial Sepsis by Modulation of Signal Transduction Pathways J. Immunol., December 15, 2003; 171(12): 6827 - 6837. [Abstract] [Full Text] [PDF]

				V. Gavrilyuk, C. Dello Russo, M. T. Heneka, D. Pelligrino, G. Weinberg, and D. L. Feinstein Norepinephrine Increases Ikappa Balpha Expression in Astrocytes J. Biol. Chem., August 9, 2002; 277(33): 29662 - 29668. [Abstract] [Full Text] [PDF]

				J. J. Watters, J. A. Sommer, Z. A. Pfeiffer, U. Prabhu, A. N. Guerra, and P. J. Bertics A Differential Role for the Mitogen-activated Protein Kinases in Lipopolysaccharide Signaling. THE MEK/ERK PATHWAY IS NOT ESSENTIAL FOR NITRIC OXIDE AND INTERLEUKIN 1beta PRODUCTION J. Biol. Chem., March 8, 2002; 277(11): 9077 - 9087. [Abstract] [Full Text] [PDF]

				T. L. Yaksh, D. M. Dirig, C. M. Conway, C. Svensson, Z. D. Luo, and P. C. Isakson The Acute Antihyperalgesic Action of Nonsteroidal, Anti-Inflammatory Drugs and Release of Spinal Prostaglandin E2 Is Mediated by the Inhibition of Constitutive Spinal Cyclooxygenase-2 (COX-2) but not COX-1 J. Neurosci., August 15, 2001; 21(16): 5847 - 5853. [Abstract] [Full Text] [PDF]