Inhibition of interleukin-5 gene expression by dexamethasone.
The effect of glucocorticoids on interleukin-5 (IL-5) gene expression was assessed in human peripheral blood mononuclear cells. IL-5 expression was stimulated by phytohaemagglutinin (PHA), IL-2, phorbol myristate acetate (PMA) or Ionomycin. A semi-quantitative assay for IL-5 gene expression was developed, based on RNA extraction and the polymerase chain reaction. IL-5 expression in response to PHA was profoundly inhibited by 10(-6) M dexamethasone, and significant inhibition was detected at doses of dexamethasone as low as 10(-9) M. When dexamethasone was added to the cells at the same time as PHA, the inhibitory effect could be detected as early as 3 hr. Dexamethasone at 10(-6) M also profoundly inhibited the IL-5 response to PMA and to IL-2, but the IL-5 response to Ionomycin was not significantly affected. These results suggest that dexamethasone may be capable of interfering with a pathway involving protein kinase C. There is increasing evidence that IL-5 may play a pathogenic role in asthma and other manifestations of acute hypersensitivity. The present findings indicate that inhibition of IL-5 expression may be one of the mechanisms whereby glucocorticoids exert their beneficial effects in diseases such as asthma.
Rolfe
F G
FG
Centre for Immunology, St Vincent's Hospital, Sydney, New South Wales, Australia.
Hughes
J M
JM
Armour
C L
CL
Sewell
W A
WA
D001483:Base Sequence; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000235:genetics*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000276:immunology; D016133:Polymerase Chain Reaction
D015848:Interleukin-5; D010835:Phytohemagglutinins; D003907:Dexamethasone