ArticleThe Journal of experimental medicine1993
Transcription of the interleukin 4 gene is regulated by multiple promoter elements.
Article in The Journal of experimental medicine, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 102 citations in OpenAlex.
- Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4.The Journal of experimental medicine · 2006Article
- Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Nuclear factor of activated T cells c is a target of p38 mitogen-activated protein kinase in T cells.Molecular and cellular biology · 2003Article
- Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression.The Journal of experimental medicine · 2002Article
- Characterization of a novel negative regulatory element in the human interleukin 4 promoter.Leukemia · 2000Article
- Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation.The EMBO journal · 1999Article
- Molecular mechanisms in T helper phenotype development.Springer seminars in immunopathology · 1999Review
- Impaired interleukin 4 signaling in T helper type 1 cells.The Journal of experimental medicine · 1998Article
- T-cell subset-specific expression of the IL-4 gene is regulated by a silencer element and STAT6.The EMBO journal · 1997Article
- Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells.Molecular and cellular biology · 1997Article
- Nitric oxide increased interleukin-4 expression in T lymphocytes.Immunology · 1997Article
- Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells.The Journal of experimental medicine · 1997Article
- Investigation of an interleukin-4 promoter polymorphism for associations with asthma and atopy.Journal of medical genetics · 1996Article
- Cytokine transcriptional events during helper T cell subset differentiation.The Journal of experimental medicine · 1996Article
- Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes.Molecular and cellular biology · 1996Article
- Nuclear factor of activated T cells is associated with a mast cell interleukin 4 transcription complex.Molecular and cellular biology · 1996Article
- Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells.Proceedings of the National Academy of Sciences of the United States of America · 1995Article
- Mercuric chloride, a chemical responsible for T helper cell (Th)2-mediated autoimmunity in brown Norway rats, directly triggers T cells to produce interleukin-4.The Journal of clinical investigation · 1995Article
- Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding.The Journal of experimental medicine · 1995Article
- Calcineurin acts in synergy with PMA to inactivate I kappa B/MAD3, an inhibitor of NF-kappa B.The EMBO journal · 1994Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of T helper cell 1 (Th1) and Th2 results in transcription of the interleukin 2 (IL-2) and IL-4 cytokine genes, respectively. Whereas many of the regulatory elements and factors responsible for IL-2 transcription in T cells are well defined, little is known about parallel mechanisms that drive transcription of the IL-4 gene. Here we have analyzed the murine IL-4 promoter, both in vivo and in a Th2 clone. 3 kb of IL-4 upstream sequence is shown to be sufficient to achieve tissue-specific and inducible expression of a thymidine kinase reporter gene in vivo in a manner that mirrors the expression of endogenous IL-4. Tissue-specific and inducible expression is also demonstrated in a Th2 clone, but not in a B cell line. Deletional and mutational analysis of the IL-4 promoter demonstrated that sequences from -100 to -28 were necessary for a transcriptional response to Concanavalin A or anti-CD3 monoclonal antibody. An overlapping, yet smaller region, spanning the sequences from -60 to -28 bp was shown to be required for the response to ionomycin. Mutation of an 8-bp region from -43 to -35 of the IL-4 promoter completely abrogated IL-4 gene transcription in response to all stimuli tested. In addition, our results show that the effects of the immunosuppressive agent Cyclosporin A map to the same DNA sequences as the positive control elements. These results identify DNA sequences that are functionally important for the control of IL-4 gene transcription both in vivo and in vitro. Although these sequences are highly conserved in the human and murine IL-4 genes, they are largely not present in the IL-2 enhancer complex. Thus, cytokine-specific cis-acting elements may be one mechanism by which these two cytokine genes are differentially regulated.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.