Increased interleukin-8 release by beta-adrenoceptor activation in human transformed bronchial epithelial cells

Br J Pharmacol. 1996 Sep;119(2):402-6. doi: 10.1111/j.1476-5381.1996.tb16000.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Bronchi / drug effects*
  • Bronchi / metabolism*
  • Bucladesine / pharmacology
  • Cell Line, Transformed
  • Cells, Cultured
  • Chemotaxis, Leukocyte / drug effects
  • Cyclic AMP / biosynthesis
  • Cyclic AMP / physiology
  • Epithelium / metabolism
  • Humans
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / metabolism*
  • Isoproterenol / pharmacology
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Adrenergic, beta / physiology*

Substances

  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Interleukin-8
  • Receptors, Adrenergic, beta
  • Bucladesine
  • Cyclic AMP
  • Isoproterenol