Comparison of the mechanisms regulating IL-5, IL-4, and three other lymphokine genes in the Th2 clone D10.G4.1.
The selective eosinophilia characteristic of asthma and parasite infections appears to be dependent on the production of interleukin-5 (IL-5) by activated T lymphocytes; however, little is known about IL-5 gene regulation. In the present study, a comparison was made of the basic mechanisms regulating mRNA levels for IL-5 and four other lymphokines that are coordinately expressed in the Th2 clone D10.G4.1 in response to concanavalin A (Con A) stimulation. Northern blot and nuclear run-off analyses indicated that IL-5 and IL-4 mRNA levels are primarily regulated at the transcriptional level. Regulation of IL-3, IL-6, and IL-10 mRNA levels involved control of mRNA stability and transcription. These three mRNAs were stabilized by cycloheximide (CHX). De novo protein synthesis was obligatory for IL-5 gene transcription and was also required for maximal transcription of the IL-4 and IL-10 genes. Expression of the IL-5, IL-6, and IL-10 genes was resistant to cyclosporine A (CsA), whereas IL-3 and IL-4 gene expression was completely inhibited, indicating the involvement of different signalling pathways in the regulation of these genes. The results indicate that the IL-5 gene and each of the other genes studied are independently regulated, providing the possibility of non-coordinate expression in vivo depending on the nature of the signals received during T cell activation.
Naora
H
H
Division of Biochemistry & Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Young
I G
IG
D000818:Animals; D002999:Clone Cells; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic
D015848:Interleukin-5; D008222:Lymphokines; D012333:RNA, Messenger; D015847:Interleukin-4