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-activating polypeptide (PACAP) act as macrophage and T-cell deactivators. Previously we established that VIP/PACAP limit T-cell activation directly, by inhibiting interleukin 2 (IL-2), and indirectly, by reducing the macrophage costimulatory functions. The nature of the IL-2 transcriptional factors affected by VIP/PACAP has not been elucidated. Here we investigate the effect of VIP on the AP-l complexes bound to several regulatory sites. VIP/PACAP downregulate 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 effects of VIP/PACAP on c-Jun and JunB expression lead to changes in the composition of the AP-l complexes, from c-Jun/Fos to JunB/Fos dimers, with a subsequent decrease in DNA binding and loss of transactivating activity.
Wang
H Y
HY
Department of Biological Sciences, Rutgers University, Newark NJ 07102, USA.
Jiang
X M
XM
Ganea
D
D
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009479:Neuropeptides / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology / Q000502:physiology*
C495402:Adcyap1 protein, mouse; D000906:Antibodies; D017252:CD3 Complex; D007376:Interleukin-2; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases