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)