REGULATION OF EXPRESSION OF THE IL-2 AND IL-5 GENES AND THE ROLE OF PROTEINS RELATED TO NUCLEAR FACTOR OF ACTIVATED T-CELLS

Cyclic adenosine monophosphate (cAMP) inhibits phorbol 12-myristate 13 -acetate (PMA)-induced IL-2 production while it inhibits IL-5 producti on at the transcriptional level in EL-4, a mouse lymphoma line. The -3 21 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 fac tor of activated T cells (NF-AT), NF-kappa B, AP-1, and octamer. With use of reporter plasmid carrying multiple copies of each element, we f ound that the construct that contained the NF-AT site was most effecti ve for responding to PMA activation and cAMP inhibition. In electropho retic mobility shift assay (EMSA), PMA-induced NF-AT binding complex w as altered by cAMP. Furthermore, overexpression of the crytoplasmic co mponent of NF-AT abrogated the inhibitory action of cAMP. These result s 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 an d cAMP in EL-4 cells. Here we identified the element IL-5P, which is r equired for maximal activation of the IL-5 promoter. We found that thi s 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 th at an NF-AT factor is involved in the regulation of IL-5 gene transcri ption.