Specific activation of human interleukin-5 depends on de novo synthesis of an AP-1 complex.
It is clear from the biology of eosinophilia that a specific regulatory mechanism must exist. Because interleukin-5 (IL5) is the key regulatory cytokine, it follows that a gene-specific control of IL5 expression must exist that differs even from closely related cytokines such as IL4. Two features of IL5 induction make it unique compared with other cytokines; first, induction by cyclic adenosine monophosphate (cAMP), which inhibits other T-cell-derived cytokines, and second, sensitivity to protein synthesis inhibitors, which have no effect on other cytokines. This study has utilized the activation of different transcription factors by different stimuli in a human T-cell line to study the role of conserved lymphokine element 0 (CLE0) in the specific induction of IL5. In unstimulated cells the ubiquitous Oct-1 binds to CLE0. Stimulation induces de novo synthesis of the AP-1 members JunD and Fra-2, which bind to CLE0. The amount of IL5 produced correlates with the production of the AP-1 complex, suggesting a key role in IL5 expression. The formation of the AP-1 complex is essential, but the rate-limiting step is the synthesis of AP-1, especially Fra-2. This provides an explanation for the sensitivity of IL5 to protein synthesis inhibitors and a mechanism for the specific induction of IL5 compared with other cytokines.
D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D051921:Fos-Related Antigen-2; D051863:Host Cell Factor C1; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis / Q000378:metabolism*; D050811:Octamer Transcription Factor-1; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D015848:Interleukin-5; D050811:Octamer Transcription Factor-1; D016376:Oligonucleotides, Antisense; C494165:POU2F1 protein, human; D011500:Protein Synthesis Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D015847:Interleukin-4; D003513:Cycloheximide; D000242:Cyclic AMP