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TNF-alpha, inefficient by itself, potentiates IL-1beta-induced PGHS-2 expression in human pulmonary microvascular endothelial cells: requirement of NF-kappaB and p38 MAPK pathways.
Br J Pharmacol. 2002 Aug; 136(7):1005-14.BJ

Abstract

1: Prostaglandin H synthase-2 (PGHS-2), is an inducible enzyme involved in various inflammatory responses. We established here that interleukin-1beta (IL-1beta) but not tumour necrosis factor-alpha (TNF-alpha) increased its expression in human pulmonary microvascular endothelial cells (HPMEC). However, associated with IL-1beta, TNF-alpha greatly potentiated this enzyme induction. 2: Although unable to induce PGHS-2 expression by itself, TNF-alpha promoted a similar transcription nuclear factor-kappaB (NF-kappaB) activation to IL-1beta. This effect was more pronounced when cells were co-exposed to both cytokines. HPMEC pre-treatment with MG-132, a proteasome inhibitor, prevented NF-kappaB activation as well as more distal signalling response, indicating that NF-kappaB activation is required but not sufficient for PGHS-2 expression. 3: Both IL-1beta and TNF-alpha failed to activate c-Jun NH2-terminal kinase (JNK). In addition, PD98059, a p42/44 mitogen-activated protein kinase (MAPK) phosphorylation inhibitor, did not decrease PGHS-2 expression. However, SB 203580, a p38 MAPK inhibitor, suppressed PGHS-2 induction by IL-1beta alone or combined with TNF-alpha, demonstrating that p38 MAPK but not p42/44 MAPK or JNK cascades are required for PGHS-2 up-regulation. 4: Finally, TNF-alpha, unlike IL-1beta, was unable to promote p38 MAPK phosphorylation, indicating that the failure of TNF-alpha to induce PGHS-2 expression is linked, at least in part, to its inability to activate p38 MAPK signalling pathway. Altogether, these data enhanced our understanding of PGHS-2 regulation in HPMEC and emphasize the heterogeneity of cellular responses to proinflammatory cytokines.

Authors+Show Affiliations

Unité de Pharmacologie Cellulaire, Unité Associée, Institut Pasteur-INSERM U 485, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12145100

Citation

Said, Fatima Ait, et al. "TNF-alpha, Inefficient By Itself, Potentiates IL-1beta-induced PGHS-2 Expression in Human Pulmonary Microvascular Endothelial Cells: Requirement of NF-kappaB and P38 MAPK Pathways." British Journal of Pharmacology, vol. 136, no. 7, 2002, pp. 1005-14.
Said FA, Werts C, Elalamy I, et al. TNF-alpha, inefficient by itself, potentiates IL-1beta-induced PGHS-2 expression in human pulmonary microvascular endothelial cells: requirement of NF-kappaB and p38 MAPK pathways. Br J Pharmacol. 2002;136(7):1005-14.
Said, F. A., Werts, C., Elalamy, I., Couetil, J. P., Jacquemin, C., & Hatmi, M. (2002). TNF-alpha, inefficient by itself, potentiates IL-1beta-induced PGHS-2 expression in human pulmonary microvascular endothelial cells: requirement of NF-kappaB and p38 MAPK pathways. British Journal of Pharmacology, 136(7), 1005-14.
Said FA, et al. TNF-alpha, Inefficient By Itself, Potentiates IL-1beta-induced PGHS-2 Expression in Human Pulmonary Microvascular Endothelial Cells: Requirement of NF-kappaB and P38 MAPK Pathways. Br J Pharmacol. 2002;136(7):1005-14. PubMed PMID: 12145100.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF-alpha, inefficient by itself, potentiates IL-1beta-induced PGHS-2 expression in human pulmonary microvascular endothelial cells: requirement of NF-kappaB and p38 MAPK pathways. AU - Said,Fatima Ait, AU - Werts,Catherine, AU - Elalamy,Ismaïl, AU - Couetil,Jean-Paul, AU - Jacquemin,Claude, AU - Hatmi,Mohamed, PY - 2002/7/30/pubmed PY - 2003/4/1/medline PY - 2002/7/30/entrez SP - 1005 EP - 14 JF - British journal of pharmacology JO - Br J Pharmacol VL - 136 IS - 7 N2 - 1: Prostaglandin H synthase-2 (PGHS-2), is an inducible enzyme involved in various inflammatory responses. We established here that interleukin-1beta (IL-1beta) but not tumour necrosis factor-alpha (TNF-alpha) increased its expression in human pulmonary microvascular endothelial cells (HPMEC). However, associated with IL-1beta, TNF-alpha greatly potentiated this enzyme induction. 2: Although unable to induce PGHS-2 expression by itself, TNF-alpha promoted a similar transcription nuclear factor-kappaB (NF-kappaB) activation to IL-1beta. This effect was more pronounced when cells were co-exposed to both cytokines. HPMEC pre-treatment with MG-132, a proteasome inhibitor, prevented NF-kappaB activation as well as more distal signalling response, indicating that NF-kappaB activation is required but not sufficient for PGHS-2 expression. 3: Both IL-1beta and TNF-alpha failed to activate c-Jun NH2-terminal kinase (JNK). In addition, PD98059, a p42/44 mitogen-activated protein kinase (MAPK) phosphorylation inhibitor, did not decrease PGHS-2 expression. However, SB 203580, a p38 MAPK inhibitor, suppressed PGHS-2 induction by IL-1beta alone or combined with TNF-alpha, demonstrating that p38 MAPK but not p42/44 MAPK or JNK cascades are required for PGHS-2 up-regulation. 4: Finally, TNF-alpha, unlike IL-1beta, was unable to promote p38 MAPK phosphorylation, indicating that the failure of TNF-alpha to induce PGHS-2 expression is linked, at least in part, to its inability to activate p38 MAPK signalling pathway. Altogether, these data enhanced our understanding of PGHS-2 regulation in HPMEC and emphasize the heterogeneity of cellular responses to proinflammatory cytokines. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/12145100/TNF_alpha_inefficient_by_itself_potentiates_IL_1beta_induced_PGHS_2_expression_in_human_pulmonary_microvascular_endothelial_cells:_requirement_of_NF_kappaB_and_p38_MAPK_pathways_ L2 - https://doi.org/10.1038/sj.bjp.0704811 DB - PRIME DP - Unbound Medicine ER -