Interleukin-5 receptor alpha chain mRNA is down-regulated by transforming growth factor beta 1.
Interleukin-5 is a T cell-derived cytokine with actions restricted to the eosinophil/basophil lineage and a subset of murine B cells. High affinity receptors have been identified and shown to comprise an IL-5-specific alpha chain (IL-5R alpha) in association with a beta chain which is shared with the receptors for IL-3 and GM-CSF. Nothing is currently known of the factors which regulate the transcription and subsequent expression of the IL-5 receptor alpha chain; this study was undertaken, therefore, in order to identify agents which modulate IL-5R alpha mRNA levels, with the goal of understanding the regulation of this gene in vivo. The human IL-5-dependent erythroleukemia TF-1 was used as a source of mRNA which was analysed by northern blotting using a cDNA probe for IL-5R alpha. A range of cytokines and pharmacological agents were used in 20 hour cultures of TF-1 followed by northern analysis. Of these, only TGF-beta 1 and PMA showed any effect, which was a selective downregulation, although the PMA displayed some cytotoxicity over the long culture period. The remainder (interleukins 1 to 11, G-CSF, GM-CSF, LIF, SCF, erythropoetin, IFN-gamma, RANTES, MIP-1 alpha, FGF, EGF, PDGF, dexamethasone, forskolin, retinoic acid and cyclosporin A) failed to alter expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Zanders
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Glaxo Institute for Molecular Biology S.A., Geneva, Switzerland.
D001483:Base Sequence; D005576:Colforsin / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053649:Receptors, Interleukin-5; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006133:Growth Substances; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D016212:Transforming Growth Factor beta; D005576:Colforsin; D014212:Tretinoin; D003907:Dexamethasone; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate