Increased interleukin-8 release by beta-adrenoceptor activation in human transformed bronchial epithelial cells.
1. The effect of beta-adrenoceptor activation on release of the neutrophil chemoattractant, interleukin-8 (IL-8), was examined in human transformed bronchial epithelial cells (16HBE cells). 2. The combined beta 1- and beta 2-adrenoceptor agonist, isoprenaline, time- (100 nM, 2-18 h) and concentration- (1-30 nM) dependently increased IL-8 protein content in the cell culture supernatant as measured by an enzyme immunosorbent assay standardized for DNA by fluoro-colorimetry. 3. Isoprenaline (1-100 nM, 15 min) increased cyclic AMP concentration-dependently. 4. The effect of isoprenaline (100 nM) was inhibited by the beta-adrenoceptor blocker propranolol (10 microM). The maximum magnitude of IL-8 increase caused by beta-adrenoceptor activation was 40% of that caused by the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha 100 ng ml-1). 5. The selective beta 2-adrenoceptor agonist salbutamol (1 microM), increased IL-8 protein similarly to isoprenaline and the cyclic AMP analogue, dibutyryl cyclic AMP (1 mM) produced a corresponding effect. 6. Pretreatment with isoprenaline (100 nM) followed by TNF-alpha (20 ng ml-1) increased IL-8 additively. 7. In conclusion, beta-adrenoceptor stimulation increased the release of the neutrophil chemoattractant, IL-8 in 16HBE cells, via an increase in intracellular cyclic AMP. beta-adrenoceptor stimulation adds to the IL-8 increase caused by the pro-inflammatory cytokine TNF-alpha. If this mechanism exists in vivo, beta-adrenoceptor activation may increase neutrophil chemotaxis into the airways.
Lindén
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A
Department of Respiratory Medicine, Göteborg University, Gothenburg, Sweden.
D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis / Q000502:physiology; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology*
D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D016209:Interleukin-8; D011943:Receptors, Adrenergic, beta; D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol