Transcriptional control of the IL-5 gene by human helper T cells: IL-5 synthesis is regulated independently from IL-2 or IL-4 synthesis.
BACKGROUND
IL-5 is fundamentally involved in eosinophilic inflammation. Control of IL-5 production may be effective for the management of allergic diseases.


OBJECTIVE
We aimed to find the transcriptional mechanisms that regulate the IL-5 gene to selectively control IL-5 synthesis.


METHODS
Allergen-specific T-cell clones and T-cell hybridomas were established from the peripheral blood lymphocytes of patients with asthma, and the transcriptional regulation of the IL-5 gene was investigated with transient transfection and electrophoretic mobility shift analysis.


RESULTS
A human IL-5 promoter/enhancer-luciferase gene construct, pIL-5(-511)Luc, was transcribed on activation of IL-5-producing T-cell clones, but not IL-5-nonproducing clones. pIL-5(-511)Luc was transcribed by T-cell hybridomas derived from fusion between IL-5-producing T-cell clones and an IL-5 gene-nonexpressing T-cell line, but not by hybridomas derived from IL-5-nonproducing T-cell clones. IL-5 synthesis was not only induced by T-cell receptor stimulation but also by IL-2 receptor stimulation. Binding of NF-AT, NF-kappaB, and AP-1 was induced by T-cell receptor (TcR) stimulation, although there was no significant upregulation of binding by IL-2 stimulation.


CONCLUSIONS
IL-5 synthesis by human helper T cells is regulated at the transcriptional level. A unique transcriptional mechanism distinct from those regulating the IL-2 or IL-4 genes seems to control the IL-5 gene. Selective regulation of IL-5 gene transcription may be useful for treating eosinophlic inflammation.
D001249:Asthma / Q000473:pathology; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D006825:Hybridomas / Q000473:pathology; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics*; D016350:Leucine Zippers; D016328:NF-kappa B / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D013601:T-Lymphocytes; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology