β2-Adrenoceptor agonists inhibit release of eosinophil-activating cytokines from human airway smooth muscle cells
Autor: | Tak H. Lee, Stuart J John Hirst, Matthew P Hallsworth, Charles H C Twort |
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Rok vydání: | 2001 |
Předmět: |
Pharmacology
Eotaxin Agonist medicine.medical_specialty Forskolin medicine.drug_class medicine.medical_treatment Propranolol respiratory system Biology chemistry.chemical_compound Cytokine Endocrinology chemistry Internal medicine Isoprenaline medicine Tumor necrosis factor alpha Interleukin 8 medicine.drug |
Zdroj: | British Journal of Pharmacology. 132:729-741 |
ISSN: | 0007-1188 |
DOI: | 10.1038/sj.bjp.0703866 |
Popis: | 1. Airway smooth muscle (ASM) is a potential source of multiple pro-inflammatory cytokines during airway inflammation. beta-Adrenoceptor agonist hyporesponsiveness is a characteristic feature of asthma, and interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha are implicated in its cause. Here, the capacity of beta-adrenoceptor agonists to prevent release of GM-CSF, RANTES, eotaxin and IL-8, elicited by IL-1 beta or TNF alpha, was examined in human ASM cells. 2. Isoprenaline (approximately EC(50) 150 nM), a non-selective beta-adrenoceptor agonist, and salbutamol ( approximately EC(50) 25 nM), a selective beta(2)-adrenoceptor agonist, attenuated release of GM-CSF, RANTES and eotaxin, but not IL-8 (EC(50) >1 microM). The maximum extent of attenuation was RANTES > or = eotaxin > GM-CSF >> IL-8, and was prevented by either propranolol (1 microM), a non-selective beta-adrenoceptor antagonist, or ICI 118511 (IC(50) 15 nM), a selective beta(2)-adrenoceptor antagonist. 3. The cyclic AMP-elevating agents, dibutyryl cyclic AMP ( approximately EC(50) 135 microM), forskolin ( approximately EC(50) 530 nM) and cholera toxin ( approximately EC(50) 575 pg ml(-1)) abolished IL-1 beta-induced release of GM-CSF, RANTES and eotaxin, but not IL-8. 4. IL-1 beta (1 ng ml(-1)) attenuated early increases (up to 1 h) in cyclic AMP formation induced by salbutamol (1 microM), but not by forskolin (10 microM). The cyclo-oxygenase inhibitor, indomethacin (1 microM) prevented later increases (3 - 12 h) in IL-1 beta-stimulated cyclic AMP content, but did not prevent the attenuation by salbutamol of IL-1 beta-induced cytokine release. 5. We conclude in human ASM cells that activation of beta(2)-adrenoceptors and generation of cyclic AMP is negatively-linked to the release, elicited by IL-1 beta or TNF alpha, of eosinophil-activating cytokines such as GM-CSF, RANTES and eotaxin, but not IL-8. |
Databáze: | OpenAIRE |
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