期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 188, 期 5, 页码 1113-1119出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2018.01.006
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资金
- Swedish Research Council in Medicine and Health [11550, 2013-03316]
- Evy and Gunnar Sandberg Foundation
- Swedish Heart-Lung Foundation [20130507]
- Crafoord Foundation
- Greta and John Kock Foundation
- Alfred Osterlund Foundation
- Royal Physiographical Society in Lund
- Medical Faculty of Lund University, ALF
- Swedish Foundation of Strategic Research [SBE13-0130]
- AnaMar AB
- Swedish Research Council [2013-03316] Funding Source: Swedish Research Council
- Vinnova [2013-03316] Funding Source: Vinnova
- Swedish Foundation for Strategic Research (SSF) [SBE13-0130] Funding Source: Swedish Foundation for Strategic Research (SSF)
Serotonin [5-hydroxyttyptamine (5-HT)] is associated with several chronic pulmonary diseases, recognizing 5-HT2 receptor antagonists as potential inhibitors of tissue remodeling. However, the effects of 5-HT2 receptors, especially 5-HT2B receptors on airway function and remodeling, are unclear. We investigated the role of 5-HT2B receptors on airway smooth muscle contractility and remodeling processes. Murine precision-cut lung slices were pretreated with 5-HT2B receptor antagonists (EXT5, EXT9, RS 127445, and PRX 08066), as well as ketanserin (5-HT2A/2C receptor antagonist) (1, 10 mu mol/L), before addition of cumulative concentrations of 5-HT to induce bronchoconstriction. Remodeling effects after treatment with 10 mu mol/L 5-HT and 5-HT2 receptor antagonists were further studied in distal lung tissue by examining release of profibrotic transforming growth factor (TGF)-beta 1 and proliferation of human bronchial smooth muscle cells (HBSMCs). 5-HT induced bronchoconstriction was significantly reduced by EXT5, EXT9, and ketanserin, but not by RS 127445 or PRX 08066. The 5-HT2B receptor antagonists significantly reduced TGF-beta 1 release. 5-HT, in combination with TGF-beta 1, increased proliferation of HBSMCs, a process reduced by EXT5 and EXT9. Our results indicate that EXT5 and EXT9 may relieve bronchoconstriction in murine airways and serve as an add-on effect in attenuating pulmonary remodeling by improving airway function. The antiproliferative effect on HBSMCs and the inhibition of TGF-beta 1 release further support a role of 5-HT2B receptors in pathologic remodeling processes.
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