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

NF kappa B has been implicated as a downstream effector of G alpha q-couple d receptor signaling, but whether these and cytokine receptors activate NF kappa B similarly remains unclear. Stimulation of rat vascular smooth muscl e cell G alpha q-coupled P2Y nucleotide receptors with UTP induces lucifera se transcription from a sensitive and specific NF kappa B dependent promote r. However. these responses are only similar to 15% of that to the referenc e cytokine IL-1 beta. IL-1 beta is a powerful stimulator of I kappa B alpha degradation, RelA nuclear import, and isoform specific NF kappa B enhancer binding in vitro, responses that are not detectable after P2Y receptor sti mulation. Expression of two trans-dominant NF kappa B polypeptides suppress es induction of the NF kappa B reporter and also IL-1 beta stimulated monoc yte chemoattractant-1 mRNA, which is not induced by UTP. In contrast, UTP i nduces higher expression of the endogenous COX-2 and IL-6 mRNAs than does I L-1 beta, implying that G alpha q-coupled receptor evokes additional NF kap pa B-independent transcription factors in regulating these two genes. P2Y r eceptors are as effective as the reference growth factor PDGF-BB at inducin g CREB, AP-1, SRE and NFAT transcription, which are largely unaffected by I L-1 beta treatment. NF kappa B is less efficiently activated then several o ther transcriptional effecters of G alpha q-coupled receptor signaling in v ascular smooth muscle cells, and is instead preferentially activated by inf lammatory cytokines. (C) 2000 Academic Press.