Corticosteroids differentially regulate secretion of IL-6, IL-8, and G-CSF by a human bronchial epithelial cell line.
Human airway epithelial cells play an active role in modulating airway inflammation by elaborating a variety of proinflammatory molecules, including cytokines. The purpose of this study was to define the role of corticosteroids in the regulation of cytokine gene transcription and secretion by human bronchial epithelial cells. In particular, we assessed whether dexamethasone was capable of inhibiting the tumor necrosis factor-alpha (TNF-alpha)-mediated secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte colony-stimulating factor (G-CSF) by a human bronchial epithelial cell line (BEAS-2B). Stimulation with 20 ng/ml of TNF-alpha resulted in significant increases in secretion 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 dependent and specific. In addition, stimulation with TNF-alpha resulted in significant increases in the quantity of IL-6, IL-8, and G-CSF mRNA as detected by reverse-transcription polymerase chain reaction. Dexamethasone preconditioning significantly inhibited both the secretion of immunoreactive IL-6 and the accumulation of IL-6 mRNA. Although dexamethasone 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 either the secretion of immunoreactive G-CSF or the accumulation of G-CSF mRNA. In summary, our results suggest that corticosteroids have a differential effect on the regulation of cytokine secretion by human bronchial epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Levine
S J
SJ
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892.
Larivée
P
P
Logun
C
C
Angus
C W
CW
Shelhamer
J H
JH
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D015850:Interleukin-6; D016209:Interleukin-8; D015335:Molecular Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone