Evidence for post-transcriptional regulation of interleukin-5 by dexamethasone.
Interleukin-5 (IL-5) is a T helper type 2 cytokine, which is implicated in the pathogenesis of eosinophilic diseases such as asthma. Both peripheral blood mononuclear cells (PBMC) and primary human T cells display similar patterns of IL-5 expression when stimulated with both phorbol-12-myristate 13-acetate and phytohaemagglutinin. The expression of IL-5 stimulated by these agents was shown to require de novo transcription and translation. However, although dexamethasone was a potent inhibitor of both IL-5 release and messenger RNA accumulation from PBMC and T cells, dexamethasone had no effect on the luciferase activity of a reporter construct under the control of an IL-5 promoter region transiently transfected into primary human T cells. Furthermore, dexamethasone appeared to decrease the stability of IL-5 messenger RNA and this effect was dependent upon de novo transcription. Taken together, the results presented here suggest that, whilst transcriptional processes predominantly regulate IL-5 release, the mechanism by which dexamethasone inhibits IL-5 is post-transcriptional.
Staples
Karl J
KJ
Department of Thoracic Medicine, Imperial College of Science, Technology and Medicine, National Heart & Lung Institute, London, UK.
Bergmann
Martin W
MW
Barnes
Peter J
PJ
Newton
Robert
R
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005938:Glucocorticoids; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008156:Luciferases; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D015848:Interleukin-5; D012333:RNA, Messenger; D003609:Dactinomycin; D003907:Dexamethasone; D008156:Luciferases