Comparison of the mechanisms regulating IL-5, IL-4, and three other lymphokine genes in the Th2 clone D10.G4.1

• Published in: Experimental hematology Vol. 23; no. 7; p. 597
• Main Authors: Naora, H, Young, I G
• Format: Journal Article
• Language: English
• Published: Netherlands 01.07.1995
• Subjects: Animals; Clone Cells; Gene Expression Regulation; Interleukin-4 - genetics; Interleukin-4 - metabolism; Interleukin-5 - genetics; Interleukin-5 - metabolism; Lymphocyte Activation; Lymphokines - genetics; Lymphokines - metabolism; Mice; RNA, Messenger - analysis; T-Lymphocytes - metabolism; Transcription, Genetic
• ISSN: 0301-472X

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.