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Role of cyclo-oxygenase-2 induction in interleukin-1beta induced attenuation of cultured human airway smooth muscle cell cyclic AMP generation in response to isoprenaline.
Br J Pharmacol. 1998 Nov; 125(6):1320-8.BJ

Abstract

Airway smooth muscle (ASM) in human asthma shows reduced relaxation and cyclic AMP generation in response to beta-adrenoceptor agonists. IL-beta attenuates cyclic AMP generation but the underlying mechanism is unclear. We have reported that IL-1beta induces cyclo-oxygenase-2 (COX-2) in human ASM cells and results in a marked increase in prostanoid generation with PGE2 and PGI2 as the major products. We investigated the role of COX-2 induction and prostanoid release (measured as PGE2) in IL-1beta induced attenuation of cyclic AMP generation in response to the beta-adrenoceptor agonist isoprenaline (ISO). Pre-treatment of human ASM cells with IL-1beta significantly attenuated cyclic AMP generation in response to high concentrations of ISO (1.0-10.0 microM) in a time- and concentration-dependent manner. The effect was accompanied by a high concentration of PGE2 release. The non-selective COX inhibitor indomethacin (Ind), the selective COX-2 inhibitor NS-398, the protein synthesis inhibitors cycloheximide (CHX) and actinomycin D and the steroid dexamethasone (Dex) all abolished the PGE2 release and prevented the attenuated cyclic AMP generation. COX substrate arachidonic acid time- and concentration-dependently mimicked IL-1beta induced attenuation and the effect was prevented by the non-selective COX inhibitors Ind and flurbiprofen, but not by NS-398, CHX and Dex. In contrast to IL-1beta, TNFalpha and IFNgamma, which are ineffective in inducing COX-2 and releasing PGE2 from human ASM cells, did not affect the cyclic AMP formation. Our study demonstrates that COX-2 induction and the consequent release of prostanoids plays a crucial role in IL-1beta induced attenuation of human ASM cell cyclic AMP response to ISO.

Authors+Show Affiliations

Division of Respiratory Medicine, City Hospital, University of Nottingham.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9863663

Citation

Pang, L, et al. "Role of Cyclo-oxygenase-2 Induction in Interleukin-1beta Induced Attenuation of Cultured Human Airway Smooth Muscle Cell Cyclic AMP Generation in Response to Isoprenaline." British Journal of Pharmacology, vol. 125, no. 6, 1998, pp. 1320-8.
Pang L, Holland E, Knox AJ. Role of cyclo-oxygenase-2 induction in interleukin-1beta induced attenuation of cultured human airway smooth muscle cell cyclic AMP generation in response to isoprenaline. Br J Pharmacol. 1998;125(6):1320-8.
Pang, L., Holland, E., & Knox, A. J. (1998). Role of cyclo-oxygenase-2 induction in interleukin-1beta induced attenuation of cultured human airway smooth muscle cell cyclic AMP generation in response to isoprenaline. British Journal of Pharmacology, 125(6), 1320-8.
Pang L, Holland E, Knox AJ. Role of Cyclo-oxygenase-2 Induction in Interleukin-1beta Induced Attenuation of Cultured Human Airway Smooth Muscle Cell Cyclic AMP Generation in Response to Isoprenaline. Br J Pharmacol. 1998;125(6):1320-8. PubMed PMID: 9863663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of cyclo-oxygenase-2 induction in interleukin-1beta induced attenuation of cultured human airway smooth muscle cell cyclic AMP generation in response to isoprenaline. AU - Pang,L, AU - Holland,E, AU - Knox,A J, PY - 1998/12/24/pubmed PY - 1998/12/24/medline PY - 1998/12/24/entrez SP - 1320 EP - 8 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 125 IS - 6 N2 - Airway smooth muscle (ASM) in human asthma shows reduced relaxation and cyclic AMP generation in response to beta-adrenoceptor agonists. IL-beta attenuates cyclic AMP generation but the underlying mechanism is unclear. We have reported that IL-1beta induces cyclo-oxygenase-2 (COX-2) in human ASM cells and results in a marked increase in prostanoid generation with PGE2 and PGI2 as the major products. We investigated the role of COX-2 induction and prostanoid release (measured as PGE2) in IL-1beta induced attenuation of cyclic AMP generation in response to the beta-adrenoceptor agonist isoprenaline (ISO). Pre-treatment of human ASM cells with IL-1beta significantly attenuated cyclic AMP generation in response to high concentrations of ISO (1.0-10.0 microM) in a time- and concentration-dependent manner. The effect was accompanied by a high concentration of PGE2 release. The non-selective COX inhibitor indomethacin (Ind), the selective COX-2 inhibitor NS-398, the protein synthesis inhibitors cycloheximide (CHX) and actinomycin D and the steroid dexamethasone (Dex) all abolished the PGE2 release and prevented the attenuated cyclic AMP generation. COX substrate arachidonic acid time- and concentration-dependently mimicked IL-1beta induced attenuation and the effect was prevented by the non-selective COX inhibitors Ind and flurbiprofen, but not by NS-398, CHX and Dex. In contrast to IL-1beta, TNFalpha and IFNgamma, which are ineffective in inducing COX-2 and releasing PGE2 from human ASM cells, did not affect the cyclic AMP formation. Our study demonstrates that COX-2 induction and the consequent release of prostanoids plays a crucial role in IL-1beta induced attenuation of human ASM cell cyclic AMP response to ISO. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/9863663/Role_of_cyclo_oxygenase_2_induction_in_interleukin_1beta_induced_attenuation_of_cultured_human_airway_smooth_muscle_cell_cyclic_AMP_generation_in_response_to_isoprenaline_ L2 - https://doi.org/10.1038/sj.bjp.0702193 DB - PRIME DP - Unbound Medicine ER -