| β2-Adrenoceptor agonists inhibit release of eosinophil-activating cytokines from human airway smooth muscle cells | |
Abstract/OtherAbstract
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Airway smooth muscle (ASM) is a potential source of multiple pro-inflammatory cytokines during airway inflammation. β-Adrenoceptor agonist hyporesponsiveness is a characteristic feature of asthma, and interleukin (IL)-1β and tumour necrosis factor (TNF)-α are implicated in its cause. Here, the capacity of β-adrenoceptor agonists to prevent release of GM-CSF, RANTES, eotaxin and IL-8, elicited by IL-1β or TNFα, was examined in human ASM cells.Isoprenaline (∼EC50 150 nM), a non-selective β-adrenoceptor agonist, and salbutamol (∼EC50 25 nM), a selective β2-adrenoceptor agonist, attenuated release of GM-CSF, RANTES and eotaxin, but not IL-8 (EC50 >1 μM). The maximum extent of attenuation was RANTES ⩾ eotaxin > GM-CSF >> IL-8, and was prevented by either propranolol (1 μM), a non-selective β-adrenoceptor antagonist, or ICI 118511 (IC50 15 nM), a selective β2-adrenoceptor antagonist.The cyclic AMP-elevating agents, dibutyryl cyclic AMP (∼EC50 135 μM), forskolin (∼EC50 530 nM) and cholera toxin (∼EC50 575 pg ml−1) abolished IL-1β-induced release of GM-CSF, RANTES and eotaxin, but not IL-8.IL-1β (1 ng ml−1) attenuated early increases (up to 1 h) in cyclic AMP formation induced by salbutamol (1 μM), but not by forskolin (10 μM). The cyclo-oxygenase inhibitor, indomethacin (1 μM) prevented later increases (3 – 12 h) in IL-1β-stimulated cyclic AMP content, but did not prevent the attenuation by salbutamol of IL-1β-induced cytokine release.We conclude in human ASM cells that activation of β2-adrenoceptors and generation of cyclic AMP is negatively-linked to the release, elicited by IL-1β or TNFα, of eosinophil-activating cytokines such as GM-CSF, RANTES and eotaxin, but not IL-8. |
Authors
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Hallsworth, Matthew P, Twort, Charles H C, Lee, Tak H, Hirst, Stuart J |
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Copyright 2001, Nature Publishing Group |
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Languages : en |
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