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 Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barrios-Rodiles, M. Articles by Chadee, K. Search for Related Content PubMed PubMed Citation Articles by Barrios-Rodiles, M. Articles by Chadee, K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Novel Regulation of Cyclooxygenase-2 Expression and Prostaglandin E₂ Production by IFN- in Human Macrophages¹

Institute of Parasitology, McGill University, Quebec, Canada

Cyclooxygenase-2 (COX-2) is the inducible enzyme in macrophages responsible for high output PG production during inflammation and immune responses. Although several stimuli are known to regulate COX-2, the molecular mechanisms modulating its expression by the cytokine network are poorly understood. As IFN- priming is essential for macrophage accessory and effector cell functions, we investigated the effect of IFN- on COX-2 expression in U937 human macrophages stimulated with IL-1ß. A dose- and time-dependent increase in COX-2 mRNA and protein expression was evoked by IL-1ß, whereas the levels of COX-1, the constitutively expressed isoform, remained unaltered. Interestingly, IFN--primed cells showed 40 to 60% lower levels of COX-2 mRNA, protein expression, and PGE₂ production as compared with nonprimed cells. IFN--priming (50–500 U/ml) down-regulated COX-2 expression in a time- and dose-dependent fashion. Furthermore, IFN- inhibited COX-2 gene transcription in response to IL-1ß but not to LPS. In contrast, the rate of decay of COX-2 transcripts in nonprimed and primed macrophages was similar (t_1/2 = 3.2 h). The down-regulatory effect of IFN- on IL-1ß-induced COX-2 expression was abrogated with cycloheximide. These results highlight a novel mechanism of COX-2 regulation by IFN- at the transcriptional level, which may affect the outcome of inflammatory and immune conditions.

This article has been cited by other articles:

				R Cruz, J D Quintana-Hau, J R Gonzalez, R Tornero-Montano, L M Baiza-Duran, and L Vega Effects of an ophthalmic formulation of meloxicam on COX-2 expression, PGE2 release, and cytokine expression in a model of acute ocular inflammation Br. J. Ophthalmol., January 1, 2008; 92(1): 120 - 125. [Abstract] [Full Text] [PDF]

				F. O. Martinez, S. Gordon, M. Locati, and A. Mantovani Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression J. Immunol., November 15, 2006; 177(10): 7303 - 7311. [Abstract] [Full Text] [PDF]

				P. K. A. Mongini, J. K. Inman, H. Han, R. J. Fattah, S. B. Abramson, and M. Attur APRIL and BAFF Promote Increased Viability of Replicating Human B2 Cells via Mechanism Involving Cyclooxygenase 2. J. Immunol., June 1, 2006; 176(11): 6736 - 6751. [Abstract] [Full Text] [PDF]

				K. Nagata, K. Wada, A. Tatsuguchi, S. Futagami, K. Gudis, K. Miyake, T. Tsukui, and C. Sakamoto Heregulin-{alpha} and heregulin-beta expression is linked to a COX-2-PGE2 pathway in human gastric fibroblasts Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1243 - G1251. [Abstract] [Full Text] [PDF]

				Y. Shibata, A. Nishiyama, H. Ohata, J. Gabbard, Q. N. Myrvik, and R. A. Henriksen Differential effects of IL-10 on prostaglandin H synthase-2 expression and prostaglandin E2 biosynthesis between spleen and bone marrow macrophages J. Leukoc. Biol., April 1, 2005; 77(4): 544 - 551. [Abstract] [Full Text] [PDF]

				A. G. Granja, M. L. Nogal, C. Hurtado, V. Vila, A. L. Carrascosa, M. L. Salas, M. Fresno, and Y. Revilla The Viral Protein A238L Inhibits Cyclooxygenase-2 Expression through a Nuclear Factor of Activated T Cell-dependent Transactivation Pathway J. Biol. Chem., December 17, 2004; 279(51): 53736 - 53746. [Abstract] [Full Text] [PDF]

				T. Ohama, M. Hori, K. Sato, H. Ozaki, and H. Karaki Chronic Treatment with Interleukin-1{beta} Attenuates Contractions by Decreasing the Activities of CPI-17 and MYPT-1 in Intestinal Smooth Muscle J. Biol. Chem., December 5, 2003; 278(49): 48794 - 48804. [Abstract] [Full Text] [PDF]

				J. P. Abulencia, R. Gaspard, Z. R. Healy, W. A. Gaarde, J. Quackenbush, and K. Konstantopoulos Shear-induced Cyclooxygenase-2 via a JNK2/c-Jun-dependent Pathway Regulates Prostaglandin Receptor Expression in Chondrocytic Cells J. Biol. Chem., August 1, 2003; 278(31): 28388 - 28394. [Abstract] [Full Text] [PDF]

				X.-l. Huang, R. Pawliczak, X.-l. Yao, M. J. Cowan, M. T. Gladwin, M. J. Walter, M. J. Holtzman, P. Madara, C. Logun, and J. H. Shelhamer Interferon-gamma Induces p11 Gene and Protein Expression in Human Epithelial Cells through Interferon-gamma -activated Sequences in the p11 Promoter J. Biol. Chem., March 7, 2003; 278(11): 9298 - 9308. [Abstract] [Full Text] [PDF]

				M.-H. Wu, H.S. Sun, C.-C. Lin, K.-Y. Hsiao, P.-C. Chuang, H.-A. Pan, and S.-J. Tsai Distinct mechanisms regulate cyclooxygenase-1 and -2 in peritoneal macrophages of women with and without endometriosis Mol. Hum. Reprod., December 1, 2002; 8(12): 1103 - 1110. [Abstract] [Full Text] [PDF]

				Shuling Zhang, K. Thomas, J. C.G. Blanco, C. A. Salkowski, and S. N. Vogel The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro Innate Immunity, October 1, 2002; 8(5): 381 - 390. [Abstract] [PDF]

				X. Han, S. Chen, Y. Sun, J. L. Nadler, and D. Bleich Induction of Cyclooxygenase-2 Gene in Pancreatic {beta}-Cells by 12-Lipoxygenase Pathway Product 12-Hydroxyeicosatetraenoic Acid Mol. Endocrinol., September 1, 2002; 16(9): 2145 - 2154. [Abstract] [Full Text] [PDF]

				F. Hertelendy, M. Molnar, and R. Romero Interferon Gamma Antagonizes Interleukin-1{beta}-Induced Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Myomaterial Cells Reproductive Sciences, July 1, 2002; 9(4): 215 - 219. [Abstract] [PDF]

				M. Hori, M. Kita, S. Torihashi, S. Miyamoto, K.-J. Won, K. Sato, H. Ozaki, and H. Karaki Upregulation of iNOS by COX-2 in muscularis resident macrophage of rat intestine stimulated with LPS Am J Physiol Gastrointest Liver Physiol, May 1, 2001; 280(5): G930 - G938. [Abstract] [Full Text] [PDF]

				D. J. Berg, J. Zhang, D. M. Lauricella, and S. A. Moore IL-10 Is a Central Regulator of Cyclooxygenase-2 Expression and Prostaglandin Production J. Immunol., February 15, 2001; 166(4): 2674 - 2680. [Abstract] [Full Text] [PDF]

				M. Giroux and A. Descoteaux Cyclooxygenase-2 Expression in Macrophages: Modulation by Protein Kinase C-{alpha} J. Immunol., October 1, 2000; 165(7): 3985 - 3991. [Abstract] [Full Text] [PDF]

				J. C. G. Blanco, C. Contursi, C. A. Salkowski, D. L. DeWitt, K. Ozato, and S. N. Vogel Interferon Regulatory Factor (IRF)-1 and IRF-2 Regulate Interferon {gamma}-dependent Cyclooxygenase 2 Expression J. Exp. Med., June 19, 2000; 191(12): 2131 - 2144. [Abstract] [Full Text] [PDF]

				M. Barrios-Rodiles, G. Tiraloche, and K. Chadee Lipopolysaccharide Modulates Cyclooxygenase-2 Transcriptionally and Posttranscriptionally in Human Macrophages Independently from Endogenous IL-1{beta} and TNF-{alpha} J. Immunol., July 15, 1999; 163(2): 963 - 969. [Abstract] [Full Text] [PDF]

				L. L. Reznikov, S.-H. Kim, J. Y. Westcott, J. Frishman, G. Fantuzzi, D. Novick, M. Rubinstein, and C. A. Dinarello IL-18 binding protein increases spontaneous and IL-1-induced prostaglandin production via inhibition of IFN-gamma PNAS, February 29, 2000; 97(5): 2174 - 2179. [Abstract] [Full Text] [PDF]