CORTICOSTEROIDS DIFFERENTIALLY REGULATE SECRETION OF IL-6, IL-8, AND G-CSF BY A HUMAN BRONCHIAL EPITHELIAL-CELL LINE

Citation
Sj. Levine et al., CORTICOSTEROIDS DIFFERENTIALLY REGULATE SECRETION OF IL-6, IL-8, AND G-CSF BY A HUMAN BRONCHIAL EPITHELIAL-CELL LINE, The American journal of physiology, 265(4), 1993, pp. 120000360-120000368
Citations number
42
Categorie Soggetti
Physiology
ISSN journal
00029513
Volume
265
Issue
4
Year of publication
1993
Part
1
Pages
120000360 - 120000368
Database
ISI
SICI code
0002-9513(1993)265:4<120000360:CDRSOI>2.0.ZU;2-P
Abstract
Human airway epithelial cells play an active role in modulating airway inflammation by elaborating a variety of proinflammatory molecules, i ncluding cytokines. The purpose of this study was to define the role o f corticosteroids in the regulation of cytokine gene transcription and secretion by human bronchial epithelial cells. In particular, we asse ssed whether dexamethasone was capable of inhibiting the tumor necrosi s factor-alpha (TNF-alpha)-mediated secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte colony-stimulating factor (G1-C SF) by a human bronchial epithelial cell line (BEAS-2B). Stimulation w ith 20 ng/ml of TNF-alpha resulted in significant increases in secreti on of immunoreactive IL-6, IL-8, and G-CSF that were maximal at 24 h. TNF-alpha-mediated IL-6, IL-8, and G-CSF secretion was concentration d ependent and specific. In addition, stimulation with TNF-alpha resulte d in significant increases in the quantity of IL-6, IL-8, and G-CSF mR NA as detected by reverse-transcription polymerase chain reaction. Dex amethasone preconditioning significantly inhibited both the secretion of immunoreactive IL-6 and the accumulation of IL-6 mRNA. Although dex amethasone appeared to reduce both the secretion of immunoreactive IL- 8 and accumulation of IL-8 mRNA, the inhibitory effects did not reach statistical significance. Finally, dexamethasone did not inhibit eithe r the secretion of immunoreactive G-CSF or the accumulation of G-CSF m RNA. In summary, our results suggest that corticosteroids have a diffe rential effect on the regulation of cytokine secretion by human bronch ial epithelial cells. Although corticosteroids may ameliorate airway i nflammation by inhibition of IL-6 secretion, dexamethasone did not pre vent the TNF-alpha-mediated increases in IL-8 and G-CSF secretion. Thi s represents a potential mechanism by which corticosteroids may fail t o downregulate the chemotaxis, activation, and survival of neutrophils in inflammatory airway disorders. These cytokine pathways and their r egulatory mechanisms may have important roles in the pathogenesis and therapy of inflammatory airway disorders.