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
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.