Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2001, PMID: 11029467

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit nuclear factor-kappa B-dependent gene activation at multiple levels in the human monocytic cell line THP-1.

Delgado, M; Ganea, D

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) suppress monocyte/macrophage production of proinflammatory agents. The transcription factor NF-kappa B regulates the transcription of most agents. VIP/PACAP inhibit NF-kappa B transactivation in the lipopolysaccharide-stimulated human monocytic cell line THP-1 at multiple levels. First, VIP/PACAP inhibit p65 nuclear translocation and NF-kappa B DNA binding by stabilizing the inhibitor I kappa B alpha. Second, VIP/PACAP induce phosphorylation of the CRE-binding protein (CREB) and its binding to the CREB-binding protein (CBP). This results in a decrease in p65.CBP complexes, which further reduces NF-kappa B transactivation. Third, VIP and PACAP reduce the phosphorylation of the TATA box-binding protein (TBP), resulting in a reduction in TBP binding to both p65 and the TATA box. All these effects are mediated through the specific receptor VPAC1. The cAMP/cAMP-dependent protein kinase pathway mediates the effects on CBP and TBP, whereas a cAMP-independent pathway is the major transducer for the effects on p65 nuclear translocation. Since NF-kappaB represents a focal point for various stimuli and induces the expression of many proinflammatory genes, its targeting by VIP and PACAP positions them as important anti-inflammatory agents. The VIP/PACAP inhibition of NF-kappa B at various levels and through different transduction pathways could offer a significant advantage over other anti-inflammatory agents.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

p65 ⊣ VIP/PACAP: " First, VIP/PACAP inhibit p65 nuclear translocation and NF-kappa B DNA binding by stabilizing the inhibitor I kappa B alpha "

p65 ⊣ VIP/PACAP: " First, VIP/PACAP inhibit p65 nuclear translocation and NF-kappa B DNA binding by stabilizing the inhibitor I kappa B alpha "

p65 ⊣ I kappa B alpha: " First, VIP/PACAP inhibit p65 nuclear translocation and NF-kappa B DNA binding by stabilizing the inhibitor I kappa B alpha "

NF-kappa B ⊣ VIP/PACAP: " First, VIP/PACAP inhibit p65 nuclear translocation and NF-kappa B DNA binding by stabilizing the inhibitor I kappa B alpha "

NF-kappa B ⊣ VIP/PACAP: " First, VIP/PACAP inhibit p65 nuclear translocation and NF-kappa B DNA binding by stabilizing the inhibitor I kappa B alpha "

NF-kappa B ⊣ I kappa B alpha: " First, VIP/PACAP inhibit p65 nuclear translocation and NF-kappa B DNA binding by stabilizing the inhibitor I kappa B alpha "

VIP/PACAP → CRE binding protein ( CREB ): " Second, VIP/PACAP induce phosphorylation of the CRE binding protein ( CREB ) and its binding to the CREB binding protein (CBP) "

VIP/PACAP → CREB binding protein (CBP): " Second, VIP/PACAP induce phosphorylation of the CRE binding protein ( CREB ) and its binding to the CREB binding protein (CBP) "

CRE binding protein ( CREB ) → VIP/PACAP: " Second, VIP/PACAP induce phosphorylation of the CRE binding protein ( CREB ) and its binding to the CREB binding protein (CBP) "

CREB binding protein (CBP) → VIP/PACAP: " Second, VIP/PACAP induce phosphorylation of the CRE binding protein ( CREB ) and its binding to the CREB binding protein (CBP) "

TATA box binding protein (TBP) ⊣ VIP: " Third, VIP and PACAP reduce the phosphorylation of the TATA box binding protein (TBP) , resulting in a reduction in TBP binding to both p65 and the TATA box "

TATA box binding protein (TBP) ⊣ PACAP: " Third, VIP and PACAP reduce the phosphorylation of the TATA box binding protein (TBP) , resulting in a reduction in TBP binding to both p65 and the TATA box "

NF-kappa B ⊣ VIP/PACAP: " The VIP/PACAP inhibition of NF-kappa B at various levels and through different transduction pathways could offer a significant advantage over other anti-inflammatory agents "

NF-kappa B ⊣ VIP/PACAP: " The VIP/PACAP inhibition of NF-kappa B at various levels and through different transduction pathways could offer a significant advantage over other anti-inflammatory agents "

Manually curated Databases

No curated data.