RGD Reference Report - PGE2 amplifies the effects of IL-1beta on vascular smooth muscle cell de-differentiation: a consequence of the versatility of PGE2 receptors 3 due to the emerging expression of adenylyl cyclase 8. - Rat Genome Database

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PGE2 amplifies the effects of IL-1beta on vascular smooth muscle cell de-differentiation: a consequence of the versatility of PGE2 receptors 3 due to the emerging expression of adenylyl cyclase 8.

Authors: Clement, N  Glorian, M  Raymondjean, M  Andreani, M  Limon, I 
Citation: Clement N, etal., J Cell Physiol. 2006 Sep;208(3):495-505.
RGD ID: 2312769
Pubmed: (View Article at PubMed) PMID:16741924
DOI: Full-text: DOI:10.1002/jcp.20673

Transition of vascular smooth muscle cells from a contractile/quiescent to a secretory/proliferative phenotype is one of the critical steps in atherosclerosis and is instigated by pro-inflammatory cytokines released from macrophages that have infiltrated into the vascular wall. In most inflammatory diseases, cell activation induced by these compounds leads to a massive production of type E2 prostaglandin (PGE2) which often takes over and even potentiates the pro-inflammatory cytokine-related effects. To evaluate PGE2 incidence on atheroma plaque development, we investigated whether and how this compound could enhance the dedifferentiation of smooth muscle cells initially induced by interleukin-1beta (IL-1beta). To address this issue, we took advantage of vascular smooth muscle cells in primary culture and tracked two markers: PLA2 secretion and alpha-actin filament disorganization. In such a context, we found that PGE2 synergizes with IL-1beta to further enhance the phenotype transition of smooth muscle cells, through cAMP-protein kinase A. As indicated by pharmacological studies, the full PGE2-dependent potentiation of IL-1beta induced PLA2 secretion is associated with a change of regulation exerted by the subtypes 3 G(i)-coupled PGE2 receptors toward adenylyl cyclase(s) activated by the subtype 4 G(s)-linked PGE2 receptor. Whereas on contractile cells, stimulated subtypes 3 inhibit type 4-dependent PLA2 secretion, this negative regulation is switched to positive on IL-1beta-treated cells. Using real time PCR, pharmacological tools and small interfering RNA (siRNA), we demonstrated that the different integration of PGE2 signals depends on the upregulation of calcium/calmodulin stimulable adenylyl cyclase 8.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component
membrane  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Adcy8  (adenylate cyclase 8)
Gnai1  (G protein subunit alpha i1)
Gnai2  (G protein subunit alpha i2)
Gnai3  (G protein subunit alpha i3)


Additional Information