Regulation of the expression of the soluble and membrane forms of the murine IL-4 receptor.
The actions of interleukin-4 (IL-4) in vivo are likely to be positively influenced by the expression of membrane IL-4 receptors (mIL-4R) on target cells and negatively by the concentration of soluble IL-4 receptors (sIL-4R) in the extracellular environment. Inasmuch as the two forms of the mouse IL-4R are differentially encoded by alternatively spliced mRNA transcripts, the purpose of this work was to determine how their expression is regulated by IL-4 and T cell activation and whether there is preferential expression of one type of transcript over the other. In this study, the expression of sIL-4R and mIL-4R transcripts was analyzed by a semiquantitative RT-PCR method in resting and mitogen-activated splenic cells. Irrespectively of the state of cell activation, IL-4 up-regulated the levels of both types of mRNA with similar kinetics and dose-response curves. In contrast, ConA failed to enhance the steady-state levels of sIL-4R or mIL-4R transcripts despite increased expression at the protein level, suggesting that sIL-4R expression is also regulated at levels other than transcription. Western blot analysis of supernatants of IL-4- and ConA-stimulated spleen cells substantiated the presence of sIL-4R molecules derived by translation of sIL-4R-specific transcripts, thus confirming the importance of this mechanism for the generation of sIL-4R molecules in normal cells. These results indicate that the sIL-4R- and mIL-4R-specific transcripts are normally regulated in a parallel manner and further suggest that expression of both forms of the IL-4R is controlled at multiple levels (i.e., transcriptional and posttranscriptional).
Chilton
P M
PM
Department of Microbiology and Immunology, University of Louisville, Kentucky 40292, USA.
Fernandez-Botran
R
R
D017398:Alternative Splicing; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D013154:Spleen / Q000378:metabolism; D014158:Transcription, Genetic
D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4