The effects of cyclosporin A, dexamethasone and other immunomodulatory drugs on induced expression of IL-3, IL-4 and IL-8 mRNA in a human mast cell line.
We examined by RT-PCR the effect of a number of immunomodulatory compounds on cytokine gene expression at the level of mRNA in the HMC-1 human leukemic mast cell line. Resting cells expressed relatively low constitutive levels of mRNA for the cytokine genes IL-3, IL-4 and IL-8, and mRNA levels for each of these cytokines were significantly enhanced after 4-h stimulation with the calcium ionophore ionomycin. Treatment of the cells with the immunosuppressant CsA at 10(-5) M produced a significant inhibition of ionomycin-induced expression of IL-3, IL-4 and IL-8 mRNA, and at 10(-6) M produced a significant inhibition of induced expression of IL-3 and IL-8 but not IL-4. At both concentrations of CsA, expression of IL-3 was inhibited to a greater extent than that of the other two cytokines. Treatment of the cells with the corticosteroid DEX at 10(-5) M but not 10(-6) M significantly reduced the ionomycin-induced expression of IL-3 but not IL-4 or IL-8 mRNA. Progesterone and methotrexate were both inactive in modulation of induced cytokine expression in this cell line. In conclusion, this study shows that cytokine expression, particularly of IL-3, is inhibited in a human mast cell line by CsA and DEX. These findings may be relevant to the anti-allergic action of these drugs.
Warbrick
E V
EV
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Thomas
A L
AL
Williams
C M
CM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007377:Interleukin-3 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007166:Immunosuppressive Agents; D007377:Interleukin-3; D016209:Interleukin-8; D007378:Interleukins; D012333:RNA, Messenger; D015847:Interleukin-4; D011374:Progesterone; D003907:Dexamethasone; D016572:Cyclosporine; D008727:Methotrexate