Riihimäki M, Raine A, Art T, Lekeux P, Couëtil L, Pringle J
Department of Clinical Sciences, Section of Large Animal Surgery and Medicine, Equine Internal Medicine, Swedish University of Agricultural Sciences, Box 7054, SE-750 07 Uppsala, Sweden.
Vet Immunol Immunopathol. 2008 Apr 15;122(3-4):256-64. doi: 10.1016/j.vetimm.2007.12.001. Epub 2007 Dec 24.
The aim of this study was to investigate mRNA levels of cytokines in bronchial epithelium in horses with recurrent airway obstruction (RAO) during acute crisis and remission. Additionally, cytokine mRNA levels in endobronchial biopsies and bronchoalveolar lavage (BAL) cells were compared. Seven RAO horses were examined while in respiratory crisis following provocation and again while in remission after 2 months on pasture, during which time six healthy horses on pasture were also examined. Quantitative real-time PCR (RT-PCR) was used to assess mRNA expression for cytokines IL-5, IL-6, IL-8, IL-10, IL-17 and transforming growth factor beta1 (TGF-beta1) in endobronchial biopsies and bronchoalveolar lavage. Expression of IL-8 mRNA was significantly upregulated during crisis in both endobronchial biopsies and BAL cells (p=0.036), while there was a similar trend for upregulation of IL-10 mRNA only in BAL cells that approached significance (p=0.059). Moreover, during crisis the expression of IL-8 mRNA in BAL cells was positively correlated to relative IL-6 mRNA expression (r(s)=0.971, p=0.001) and bronchial epithelial expression of IL-10 and TGF-beta1 mRNA were positively correlated (r(s)=0.943, p=0.005). In comparing the relationship of mRNA expression in BAL to biopsy in individual RAO horses, there was a positive correlation with IL-6 to IL-8 mRNA expression in BAL during respiratory crisis (r(s)=0.971, p=0.001) that also correlated positively with IL-8 expression in biopsies on pasture (r(s)=0.986, p<0.0001 for both). Regarding RAO horses at pasture versus controls neither the cytokine mRNA levels in endobronchial biopsy nor in BAL cells differed significantly. These results further support previous findings that IL-8 mRNA in both BAL cells and bronchial epithelium is upregulated in RAO horses during crisis. However, apart from IL-8, it appears that expression of other cytokines, including IL-5, IL-6, IL-10, IL-17 and TGF-beta1 in bronchial epithelium does not necessarily mirror cytokine expression in BAL cells in individual horses with RAO. Accordingly, examination of markers of inflammation in endobronchial tissue provides complementary but not necessarily identical information to that obtained in BAL cells. Given the potential for repeated sampling over time bronchial biopsy can serve as an invaluable additional tool for investigation of time-dependent changes in inflammatory process in this animal model of asthma.
本研究的目的是调查复发性气道阻塞（RAO）马匹在急性发作期和缓解期支气管上皮中细胞因子的mRNA水平。此外，还比较了支气管活检组织和支气管肺泡灌洗（BAL）细胞中细胞因子的mRNA水平。对7匹RAO马匹在激发后处于呼吸危机时进行检查，在放牧2个月后处于缓解期时再次检查，同时也检查了6匹放牧的健康马匹。采用定量实时PCR（RT-PCR）评估支气管活检组织和支气管肺泡灌洗中细胞因子白细胞介素-5（IL-5）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、白细胞介素-17和转化生长因子β1（TGF-β1）的mRNA表达。在危机期间，支气管活检组织和BAL细胞中IL-8 mRNA的表达均显著上调（p=0.036），而仅在BAL细胞中IL-10 mRNA上调有类似趋势，接近显著水平（p=0.059）。此外，在危机期间，BAL细胞中IL-8 mRNA的表达与相对IL-6 mRNA的表达呈正相关（r(s)=0.971，p=0.001），支气管上皮中IL-10和TGF-β1 mRNA的表达呈正相关（r(s)=0.943，p=0.005）。在比较个体RAO马匹BAL与活检组织中mRNA表达的关系时，呼吸危机期间BAL中IL-6与IL-8 mRNA的表达呈正相关（r(s)=0.971，p=0.001），这也与放牧时活检组织中IL-8的表达呈正相关（两者r(s)=0.986，p<0.0001）。对于放牧的RAO马匹与对照组，支气管活检组织和BAL细胞中的细胞因子mRNA水平均无显著差异。这些结果进一步支持了先前的研究结果，即RAO马匹在危机期间BAL细胞和支气管上皮中的IL-8 mRNA均上调。然而，除IL-8外，在患有RAO的个体马匹中，支气管上皮中包括IL-5、IL-6、IL-10、IL-17和TGF-β1在内的其他细胞因子的表达不一定反映BAL细胞中的细胞因子表达。因此，检查支气管内组织中的炎症标志物可提供与BAL细胞中获得的信息互补但不一定相同的信息。鉴于随着时间推移进行重复采样的可能性，支气管活检可作为研究该哮喘动物模型中炎症过程时间依赖性变化的宝贵辅助工具。
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