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Induction of cyclooxygenase-2 expression in human myometrial smooth muscle cells by interleukin-1beta: involvement of p38 mitogen-activated protein kinase.
J Physiol. 1999 Oct 15; 520 Pt 2:399-406.JP

Abstract

1. Human myometrial smooth muscle cells (HMSMCs) in culture were exposed to recombinant human interleukin-1beta (IL-1beta, 10 ng ml-1) for 1 to 24 h. Cyclooxygenase-2 (COX-2) mRNA and protein were rapidly induced, with expression sustained at 24 h. 2. Cycloheximide (10 microg ml-1, 6 h) blocked IL-1beta-induced COX-2 protein expression and super-induced COX-2 mRNA expression. Induction of COX-2 mRNA and protein was blocked by dexamethasone (1 microm, 6 h). 3. IL-1beta-induced COX-2 expression was accompanied by a 3-fold increase of prostaglandin E2 release into the culture medium. 4. IL-1beta induced a transient (5-30 min) activation of p42/44 and p38 mitogen-activated protein kinase (MAPK) enzymes in HMSMCs. Activity of p38 MAPK was monitored by in-gel activity of its substrate MAP kinase-activated protein kinase-2 (MAPKAP kinase-2). Induction of MAPKAP kinase-2 activity was prevented by the p38 MAPK inhibitor SB 203580 (10 microm, 5-30 min). 5. COX-2 protein expression detected after 6 h IL-1beta stimulation was blocked by SB 203580 (10 microM). Exposure of HMSMCs to 10 ng ml-1 IL-1beta for only 30 min induced a level of COX-2 protein expression at 6 h culture similar to that detected in cells exposed to the cytokine for 6 h. 6. Exposure of cells to SB 203580 (10 microM during only the first 30 min of IL-1beta stimulation was effective in blocking COX-2 protein expression assayed after 6 h in culture. 7. This study has established that a transient activation of the p38 MAPK cascade is involved in IL-1beta-stimulated COX-2 expression in human myometrial smooth muscle cells. Induction of COX-2 by IL-1beta in HMSMCs provides support for the hypothesis that autocrine prostaglandin signalling in the myometrium, initiated by elevated intrauterine cytokine concentrations, plays a role in regulating myometrial contractility during labour.

Authors+Show Affiliations

Centre for Cardiovascular Biology and Medicine, GKT School of Biomedical Sciences, King's College London, Guy's Campus, London SE1 9RT, UK. simon.bartlett@kcl.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10523409

Citation

Bartlett, S R., et al. "Induction of Cyclooxygenase-2 Expression in Human Myometrial Smooth Muscle Cells By Interleukin-1beta: Involvement of P38 Mitogen-activated Protein Kinase." The Journal of Physiology, vol. 520 Pt 2, 1999, pp. 399-406.
Bartlett SR, Sawdy R, Mann GE. Induction of cyclooxygenase-2 expression in human myometrial smooth muscle cells by interleukin-1beta: involvement of p38 mitogen-activated protein kinase. J Physiol (Lond). 1999;520 Pt 2:399-406.
Bartlett, S. R., Sawdy, R., & Mann, G. E. (1999). Induction of cyclooxygenase-2 expression in human myometrial smooth muscle cells by interleukin-1beta: involvement of p38 mitogen-activated protein kinase. The Journal of Physiology, 520 Pt 2, 399-406.
Bartlett SR, Sawdy R, Mann GE. Induction of Cyclooxygenase-2 Expression in Human Myometrial Smooth Muscle Cells By Interleukin-1beta: Involvement of P38 Mitogen-activated Protein Kinase. J Physiol (Lond). 1999 Oct 15;520 Pt 2:399-406. PubMed PMID: 10523409.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of cyclooxygenase-2 expression in human myometrial smooth muscle cells by interleukin-1beta: involvement of p38 mitogen-activated protein kinase. AU - Bartlett,S R, AU - Sawdy,R, AU - Mann,G E, PY - 1999/10/16/pubmed PY - 1999/10/16/medline PY - 1999/10/16/entrez SP - 399 EP - 406 JF - The Journal of physiology JO - J. Physiol. (Lond.) VL - 520 Pt 2 N2 - 1. Human myometrial smooth muscle cells (HMSMCs) in culture were exposed to recombinant human interleukin-1beta (IL-1beta, 10 ng ml-1) for 1 to 24 h. Cyclooxygenase-2 (COX-2) mRNA and protein were rapidly induced, with expression sustained at 24 h. 2. Cycloheximide (10 microg ml-1, 6 h) blocked IL-1beta-induced COX-2 protein expression and super-induced COX-2 mRNA expression. Induction of COX-2 mRNA and protein was blocked by dexamethasone (1 microm, 6 h). 3. IL-1beta-induced COX-2 expression was accompanied by a 3-fold increase of prostaglandin E2 release into the culture medium. 4. IL-1beta induced a transient (5-30 min) activation of p42/44 and p38 mitogen-activated protein kinase (MAPK) enzymes in HMSMCs. Activity of p38 MAPK was monitored by in-gel activity of its substrate MAP kinase-activated protein kinase-2 (MAPKAP kinase-2). Induction of MAPKAP kinase-2 activity was prevented by the p38 MAPK inhibitor SB 203580 (10 microm, 5-30 min). 5. COX-2 protein expression detected after 6 h IL-1beta stimulation was blocked by SB 203580 (10 microM). Exposure of HMSMCs to 10 ng ml-1 IL-1beta for only 30 min induced a level of COX-2 protein expression at 6 h culture similar to that detected in cells exposed to the cytokine for 6 h. 6. Exposure of cells to SB 203580 (10 microM during only the first 30 min of IL-1beta stimulation was effective in blocking COX-2 protein expression assayed after 6 h in culture. 7. This study has established that a transient activation of the p38 MAPK cascade is involved in IL-1beta-stimulated COX-2 expression in human myometrial smooth muscle cells. Induction of COX-2 by IL-1beta in HMSMCs provides support for the hypothesis that autocrine prostaglandin signalling in the myometrium, initiated by elevated intrauterine cytokine concentrations, plays a role in regulating myometrial contractility during labour. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/10523409/Induction_of_cyclooxygenase_2_expression_in_human_myometrial_smooth_muscle_cells_by_interleukin_1beta:_involvement_of_p38_mitogen_activated_protein_kinase_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3751&date=1999&volume=520&spage=399 DB - PRIME DP - Unbound Medicine ER -