Abstract | BACKGROUND: METHODS: BALB/c mice received the 5-HTR2A inhibitor ketanserin, the 5-HTR2B inhibitor RS-127445 or the natural 5-HTR2A/2B inhibitor quercetin intraperitoneally, then were exposed to cigarette smoke for 6 or 12 weeks. Control mice received placebo and were exposed to room air or cigarette smoke. Mice were sacrificed and bronchial alveolar lavage fluid (BALF) and lung tissue samples were collected. RESULTS: Immunohistochemistry and western blot confirmed an increase in both 5-HTR2A and 5-HTR2B expression in mouse lungs after exposure to cigarette smoke for 6 and 12 weeks. Cigarette smoke induced accumulation of macrophages and neutrophils and increased levels of inflammatory cytokines, including IL-1β and TNF-ɑ, in BALF and lung tissue; these effects were inhibited by ketanserin, RS-127445 and quercetin. Pretreatment with 5-HT receptor antagonists suppressed the goblet cell hyperplasia induced by 6- or 12-week exposure to cigarette smoke, based on Alcian blue- periodic acid Schiff staining. After 12 weeks of cigarette smoke exposure, Masson's staining showed fibrosis surrounding the mouse airways, and inhibitor pretreatment significantly attenuated the thickening and collagen deposition around the small airways. CONCLUSIONS:
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Authors | Ting Yang, Hao Wang, Yuhao Li, Zijian Zeng, Yongchun Shen, Chun Wan, Yanqiu Wu, Jiajia Dong, Lei Chen, Fuqiang Wen |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 81
Pg. 106036
(Apr 2020)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 31787571
(Publication Type: Journal Article)
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Copyright | Copyright © 2019 Elsevier B.V. All rights reserved. |
Chemical References |
- Htr2a protein, mouse
- Pyrimidines
- Receptor, Serotonin, 5-HT2A
- Receptor, Serotonin, 5-HT2B
- Serotonin 5-HT2 Receptor Antagonists
- Smoke
- 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine
- Ketanserin
- Quercetin
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Topics |
- Airway Remodeling
(drug effects, immunology)
- Animals
- Bronchoalveolar Lavage Fluid
(cytology, immunology)
- Disease Models, Animal
- Humans
- Injections, Intraperitoneal
- Ketanserin
(administration & dosage)
- Lung
(drug effects, immunology, pathology)
- Male
- Mice
- Mucus
(metabolism)
- Pulmonary Disease, Chronic Obstructive
(drug therapy, immunology, pathology)
- Pyrimidines
(administration & dosage)
- Quercetin
(administration & dosage)
- Receptor, Serotonin, 5-HT2A
(metabolism)
- Receptor, Serotonin, 5-HT2B
(metabolism)
- Respiratory Mucosa
(drug effects, immunology, metabolism)
- Serotonin 5-HT2 Receptor Antagonists
(administration & dosage)
- Smoke
(adverse effects)
- Specific Pathogen-Free Organisms
- Nicotiana
(adverse effects)
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