Regulation of expression of the IL-2 and IL-5 genes and the role of proteins related to nuclear factor of activated T cells - 12/09/11
Abstract |
Cyclic adenosine monophosphate (cAMP) inhibits phorbol 12-myristate 13-acetate (PMA)-induced IL-2 production while it inhibits IL-5 production at the transcriptional level in EL-4, a mouse lymphoma line. The –321 to +46 region of the mouse IL-2 promoter is required for activation by PMA and inhibition by cAMP. This promoter region contains several elements that interact with transcription factors, such as nuclear factor of activated T cells (NF-AT), NF-κB, AP-1, and octamer. With use of reporter plasmid carrying multiple copies of each element, we found that the construct that contained the NF-AT site was most effective for responding to PMA activation and cAMP inhibition. In electrophoretic mobility shift assay (EMSA), PMA-induced NF-AT binding complex was altered by cAMP. Furthermore, overexpression of the cytoplasmic component of NF-AT abrogated the inhibitory action of cAMP. These results indicate that the NF-AT site is a target of the inhibitory action of cAMP. We have previously reported that the -1200 to +33 region of the mouse IL-5 promoter can mediate transcriptional stimulation by PMA and cAMP in EL-4 cells. Here we identified the element IL-5P, which is required for maximal activation of the IL-5 promoter. We found that this element is homologous to the binding site for NF-AT and interacted with NF-AT-related factors induced by PMA and cAMP. Thus it appears that an NF-AT factor is involved in the regulation of IL-5 gene transcription. (J ALLERGY CLIN IMMUNOL 1995;96:1126-35.)
Le texte complet de cet article est disponible en PDF.Keywords : IL-2 gene, IL-5 gene, nuclear factor of activate T cells, helper T cells, cyclic adenosine monophosphate
Abbreviations : AP-1p, Bt2, cAMP, CLE, EMSA, NF-AT, Octp, PMA, Th
Plan
![]() | From the Department of Molecular and Developmental Biology, The Institute of Medical Science. The University of Tokyo, Tokyo, Japan, a and the Department of Cell Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA.b |
![]() ![]() | Reprint requests: Ken-ichi Arai, MD, PhD, Department of Molecular and Developmental Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan. |
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Vol 96 - N° 6S
P. 1126-1135 - décembre 1995 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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