Differential regulation of vascular smooth muscle nuclear factor kappa-B by G alpha q-coupled and cytokine receptors

J Mol Cell Cardiol. 2000 Mar;32(3):391-403. doi: 10.1006/jmcc.1999.1085.

Abstract

NF kappaB has been implicated as a downstream effector of G alphaq-coupled receptor signaling, but whether these and cytokine receptors activate NF kappaB similarly remains unclear. Stimulation of rat vascular smooth muscle cell G alphaq-coupled P2Y nucleotide receptors with UTP induces luciferase transcription from a sensitive and specific NF kappaB dependent promoter. However, these responses are only;15% of that to the reference cytokine IL-1 beta. IL-1 beta is a powerful stimulator of I kappaB alpha degradation, RelA nuclear import, and isoform specific NF kappaB enhancer binding in vitro, responses that are not detectable after P2Y receptor stimulation. Expression of two trans -dominant NF kappaB polypeptides suppresses induction of the NF kappaB reporter and also IL-1 beta stimulated monocyte chemoattractant-1 mRNA, which is not induced by UTP. In contrast, UTP induces higher expression of the endogenous COX-2 and IL-6 mRNAs than does IL-1 beta, implying that G alphaq-coupled receptor evokes additional NF kappaB-independent transcription factors in regulating these two genes. P2Y receptors are as effective as the reference growth factor PDGF-BB at inducing CREB, AP-1, SRE and NFAT transcription, which are largely unaffected by IL-1 beta treatment. NF kappaB is less efficiently activated then several other transcriptional effectors of G alphaq-coupled receptor signaling in vascular smooth muscle cells, and is instead preferentially activated by inflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Becaplermin
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Cyclooxygenase 2
  • DNA-Binding Proteins / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • GTP-Binding Proteins / metabolism*
  • Humans
  • I-kappa B Proteins*
  • Interleukin-1 / metabolism
  • Interleukin-1 / pharmacology
  • Interleukin-6 / genetics
  • Isoenzymes / genetics
  • Membrane Proteins
  • Mice
  • Muscle, Smooth, Vascular / cytology
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • Platelet-Derived Growth Factor / metabolism
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-sis
  • Rats
  • Receptors, Interleukin-1 / metabolism*
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2Y2
  • Transcription Factor RelA
  • Transcription Factor RelB
  • Transcription Factors / metabolism
  • Uridine Triphosphate / metabolism
  • Uridine Triphosphate / pharmacology

Substances

  • Chemokine CCL2
  • DNA-Binding Proteins
  • I kappa B beta protein
  • I-kappa B Proteins
  • Interleukin-1
  • Interleukin-6
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • P2RY2 protein, human
  • P2ry2 protein, mouse
  • P2ry2 protein, rat
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-sis
  • RELB protein, human
  • Receptors, Interleukin-1
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y2
  • Relb protein, mouse
  • Relb protein, rat
  • Transcription Factor RelA
  • Transcription Factors
  • purinoceptor P2Y6
  • Transcription Factor RelB
  • Becaplermin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • GTP-Binding Proteins
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Uridine Triphosphate