The neuropeptides VIP and PACAP inhibit IL-2 transcription by decreasing c-Jun and increasing JunB expression in T cells

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activat ing polypeptide (PACAP) act as macrophage and T-cell deactivators. Previous ly we established that VIP/PACAP limit T-cell activation directly, by inhib iting interleukin 2 (IL-2), and indirectly, by reducing the macrophage cost imulatory functions. The nature of the IL-2 transcriptional factors affecte d by VIP/PACAP has not been elucidated. Here we investigate the effect of V IP on the AP-1 complexes bound to several regulatory sites. VIP/PACAP downr egulate c-Jun, and upregulate JunB mRNA and protein. The reduction in c-Jun correlates with the inhibition of the c-Jun N-terminal kinase (JNK). The e ffects of VIP/PACAP on c-Jun and JunB expression lend to changes in the com position of the AP-1 complexes, from c-Jun/Fos to JunB/Fos dimers, with a s ubsequent decrease in DNA binding and loss of transactivating activity. (C) 2000 Elsevier Science B.V. All rights reserved.