⌘+K

December 1, 2013Life SciencesOpen Access

Remodeling of endothelial function in atherosclerotic mice overexpressing endothelin-1 restricted to endothelium

View Full Paper

Ask AI

Bookmark

Share

Key Points

To identify the intracellular signaling cascades that mediate the synergistic stimulation of interleukin-6 gene expression by endothelin-1 and cyclic AMP in adipocytes.
Transfected 3T3-L1 adipocytes with a luciferase reporter driven by the mouse IL-6 promoter (-1310/+198) to monitor IL-6 transcriptional activation.
Treated cells with ET-1 and 8-bromo cAMP in the presence or absence of signaling inhibitors (pertussis toxin, GF109203X, U0126, N-acetylcysteine, salicylate, mithramycin A), dominant negative CREB, and c-Jun antisense oligonucleotides.
Transcriptional stimulation by ET-1 alone was blocked by pertussis toxin, GF109203X, U0126, NAC, salicylate, dn-CREB, and mithramycin A, whereas stimulation by 8-bromo cAMP alone was inhibited exclusively by dn-CREB.
The synergistic response to co-treatment with ET-1 and cAMP was abolished by GF109203X, U0126, salicylate, AS-cJun, and dn-CREB, partially reduced by pertussis toxin, and unaffected by NAC or mithramycin A.
Identification of p90 ribosomal S6 kinase as a salicylate-sensitive target indicates that synergistic IL-6 promoter activation relies on cooperative signaling through PKC, MAPK, CREB, AP-1, and RSK pathways.

Implication

In vitro study uncovers signaling pathways mediating synergistic IL-6 induction by endothelin-1 and cAMP in adipocytes, indicating involvement of PKC, MAPK, and RSK.

Abstract

No abstract yet. The journal hasn't published one we can show.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Paradis et al. (2013) studied this question.

synapsesocial.com/papers/6ab48a224fbe54468a75b9fd https://doi.org/10.1016/j.lfs.2013.12.128

View Full Paper

Ask AI

Bookmark

Share