Cytokine release and adhesion molecule expression by stimulated human bronchial epithelial cells are downregulated by salmeterol.
Summary beta2-adrenoreceptor agonists are able to modulate various aspects of airway cell functions involved in the inflammatory and repair processes characterizing a variety of respiratory disorders. Human bronchial epithelial cells (HBECs), which can act as immune effector cells and express beta2-adrenoreceptors, were used to test the effects of different concentrations (0.1-100.0 nM) of salmeterol (Salm) on adhesion molecule expression and chemokine/cytokine release. HBECs, freshly isolated from resected bronchi at the time of surgery in ex-smokers with lung cancer, constitutively expressed over 3 times more ICAM-1 than VCAM-1 (P<0.05) and secreted greater amounts of IL-8 than of GM-CSF or RANTES (P<0.001). Stimulation of HBECs with IL-4, TNF-alpha or IL-4 plus TNF-alpha-upregulated ICAM-1 expression (P<0.05) and increased GM-CSF and IL-8 secretion (P<0.05). Similarly, VCAM-1 expression was significantly increased by IL-4 plus TNF-alpha, while RANTES release was significantly enhanced by IL-4 or by IL-4 plus TNF-alpha (P<0.05), but not by TNF-alpha alone (P>0.05). Dose-response curves showed that Salm, at concentration >1.0 nM, was effective in inhibiting adhesion molecule expression and cytokine release by HBECs (P<0.05). At a Salm concentration of 10 nM the degree of inhibition observed was similar for ICAM-1 and VCAM-1 expression (37.2 +/- 9.3% and 32.9 +/- 9.6%, respectively; P>0.05), but higher for RANTES (88.4 +/- 4.4%), as compared to IL-8 (21.8 +/- 7.0%) or GM-CSF (30.1 +/- 6.6%; P<0.05, each comparison). Thus, adhesion molecules and cytokines may be expressed/released at very different levels by unstimulated or stimulated HBECs and those activities appear to be modulated by Salm.
D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D000068299:Salmeterol Xinafoate; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D001993:Bronchodilator Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D000068299:Salmeterol Xinafoate; D000420:Albuterol