Lee Hwa Young, Rhee Chin Kook, Kang Ji Young, Park Chan Kwon, Lee Sook Young, Kwon Soon Suk, Kim Young Kyoon, Yoon Hyoung Kyu
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Korean J Intern Med. 2016 Jan;31(1):89-97. doi: 10.3904/kjim.2016.31.1.89. Epub 2015 Dec 28.
BACKGROUND/AIMS: Asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Peroxisome proliferator-activated receptors have been reported to regulate inflammatory responses in many cells. In this study, we examined the effects of intranasal rosiglitazone on airway remodeling in a chronic asthma model.
We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated intranasally with rosiglitazone with or without an antagonist during OVA challenge. We determined airway inflammation and the degree of airway remodeling by smooth muscle actin area and collagen deposition.
Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, compared with control mice. Additionally, the mice developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of rosiglitazone intranasally inhibited the eosinophilic inflammation significantly, and, importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. Expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was increased in the OVA group and decreased in the rosiglitazone group. Co-treatment with GW9660 (a rosiglitazone antagonist) and rosiglitazone increased the expression of TLR-4 and NF-κB.
These results suggest that intranasal administration of rosiglitazone can prevent not only air way inf lammation but also air way remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4 and NF-κB pathways.
背景/目的：哮喘的特征为气道高反应性、炎症和重塑。据报道，过氧化物酶体增殖物激活受体可调节多种细胞中的炎症反应。在本研究中，我们检测了鼻内给予罗格列酮对慢性哮喘模型气道重塑的影响。
我们建立了一种气道重塑小鼠模型，包括平滑肌增厚，其中卵清蛋白（OVA）致敏小鼠每周两次经鼻给予OVA，持续3个月。在OVA激发期间，小鼠经鼻给予罗格列酮，同时或不同时给予拮抗剂。我们通过平滑肌肌动蛋白面积和胶原沉积来确定气道炎症和气道重塑程度。
与对照小鼠相比，长期暴露于OVA的小鼠出现持续的嗜酸性气道炎症。此外，这些小鼠出现气道重塑特征，包括支气管周围平滑肌层增厚。鼻内给予罗格列酮可显著抑制嗜酸性炎症，重要的是，可抑制长期暴露于OVA的小鼠的气道平滑肌重塑。Toll样受体（TLR）-4和活化B细胞核因子κB（NF-κB）的表达在OVA组中升高，而在罗格列酮组中降低。GW9660（一种罗格列酮拮抗剂）与罗格列酮联合治疗可增加TLR-4和NF-κB的表达。
这些结果表明，鼻内给予罗格列酮不仅可以预防气道炎症，还可以预防与慢性过敏原激发相关的气道重塑。这种有益作用是通过抑制TLR-4和NF-κB途径介导的。
