Abstract |
Adventitia is the outer part of the arterial wall where the inflammatory response often occurs. Urotensin II (UII) is a potent vasoconstrictive peptide that also promotes the inflammatory process in patients with cardiovascular disease. Leukotriene C4 ( LTC4), a lipid mediator, was recently found to play a role in the inflammatory process in the artery. We hypothesized that the adventitia is one of the resources of LTC4 and that UII may promote LTC4 production through the 5-LO (5-lipoxygenase) pathway in adventitial fibroblasts. Rat adventitial fibroblasts were isolated and incubated in serum-free medium with either UII alone or in combination with inhibitors of p38 MAPK, ERK, and UII receptors. The expression of 5-LO was detected using real-time polymerase chain reaction and Western blot. The translocation and binding activity of nuclear factor (NF)-κB were measured using immunofluorescence and electrophoretic mobility shift assay, respectively. The production of LTC4 was measured by enzyme-linked immunosorbent assay. The results indicated that: (1) adventitial fibroblasts were a source of LTC4 production; (2) UII increased the expression of the 5-LO mRNA and the protein by NF-κB activation through p38 MAPK and ERK pathways; and (3) UII promoted the LTC4 release in fibroblasts through the 5-LO pathway by p38 MAPK and ERK activations. The 5-LO pathway mediates LTC4 production, which may be a new mechanism in the pathogenesis of the vascular adventitial inflammation caused by UII.
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Authors | Xiao Dong, Xiaojin Ye, Nana Song, Jing Zhao, Beibing Di, Fen Peng, Chaoshu Tang, Wenhui Ding |
Journal | Heart and vessels
(Heart Vessels)
Vol. 28
Issue 4
Pg. 514-23
(Jul 2013)
ISSN: 1615-2573 [Electronic] Japan |
PMID | 23053343
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Inflammation Mediators
- NF-kappa B
- Protein Kinase Inhibitors
- RNA, Messenger
- Receptors, G-Protein-Coupled
- Urotensins
- Uts2r protein, rat
- Leukotriene C4
- urotensin II
- Arachidonate 5-Lipoxygenase
- Extracellular Signal-Regulated MAP Kinases
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Active Transport, Cell Nucleus
- Adventitia
(cytology, drug effects, enzymology)
- Animals
- Aorta
(cytology, drug effects, enzymology)
- Arachidonate 5-Lipoxygenase
(genetics, metabolism)
- Cells, Cultured
- Dose-Response Relationship, Drug
- Enzyme Activation
- Extracellular Signal-Regulated MAP Kinases
(antagonists & inhibitors, metabolism)
- Fibroblasts
(drug effects, enzymology)
- Inflammation Mediators
(metabolism)
- Leukotriene C4
(metabolism)
- MAP Kinase Signaling System
(drug effects)
- Male
- NF-kappa B
(metabolism)
- Protein Kinase Inhibitors
(pharmacology)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptors, G-Protein-Coupled
(drug effects, metabolism)
- Time Factors
- Urotensins
(pharmacology)
- p38 Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
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