Modulation by flunisolide of tumor necrosis factor-alpha-induced stimulation of airway epithelial cell activities related to eosinophil inflammation.
BACKGROUND
Tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine involved in the pathogenesis of asthma, displays multiple functions on a variety of cells, including bronchial epithelial cells (BECs).


OBJECTIVE
To characterize in vitro changes induced by TNF-alpha on the function of BECs that may be related to eosinophilic inflammation and to evaluate their modulation by an inhaled corticosteroid, flunisolide.


METHODS
A normal human bronchial epithelial cell line (BEAS-2B) was incubated with TNF-alpha (10 ng/ml) to evaluate (a) intercellular adhesion molecule (ICAM)-1 expression and granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-5 release by BEAS-2B; (b) eosinophil adhesion to BEAS-2B; and (c) the modulation of these activities by flunisolide (0.1 to 10 microM).


RESULTS
Stimulation of BEAS-2 with TNF-alpha generated an increase in ICAM-1 expression (p = .0012), in GM-CSF and IL-5 release (p < .01), and in eosinophil adhesion to BEAS-2B, but this latter effect did not reach statistical significance. Flunisolide at all the tested concentrations effectively inhibited ICAM-1 expression and GM-CSF and IL-5 release (p < .05). The percent inhibition induced by the highest flunisolide concentration (10 muM) for the various BEAS-2B functions was 30%, 60%, and 70%, respectively. The effect of flunisolide appeared to be related to an inhibition of "TNF-alpha-induced" ICAM-1 expression and cytokine release with little or no involvement of the "constitutive" expression and release.


CONCLUSIONS
An increase in ICAM-1 expression in BECs was found to be induced by TNF-alpha and associated with enhancement of the constitutive secretion of GM-CSF and IL-5, cytokines related to eosinophilic inflammation. The ability of flunisolide to modulate these BECs activities appears to be mostly related to the inhibition of the "TNF-alpha-induced" responses.
Boero
S
S
Pulmonary Diseases Unit, G. Gaslini Institute, Genoa, Italy.
Silvestri
M
M
Ullmann
N
N
Rossi
G A
GA
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D002448:Cell Adhesion; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives* / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D005446:Fluocinolone Acetonide; D018799:Intercellular Adhesion Molecule-1; C007734:flunisolide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor