Heinecke Lowella, Proud David, Sanders Scherer, Schleimer Robert P, Kim Jean
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
J Allergy Clin Immunol. 2008 May;121(5):1155-60. doi: 10.1016/j.jaci.2008.02.009. Epub 2008 Apr 18.
T-cell infiltration of the epithelium is a key feature of chronic rhinosinusitis and asthma. Viral infections are an important cause of disease exacerbations. We have found virus-induced expression of T cell-interacting ligands, B7 homolog costimulatory molecules, on airway epithelium.
We tested the ability of human rhinovirus (HRV) 16 and double-stranded RNA (dsRNA) to alter the expression of B7 homologs on human airway epithelial cells.
BEAS2B and primary human airway epithelial cells were exposed in vitro to dsRNA (25 microg/mL) or HRV-16, and then expression of cell-surface protein and mRNA for B7 homologs was assessed by means of flow cytometry and real-time PCR, respectively. Additionally, human subjects were infected with HRV-16 in vivo, and mRNA for B7 homologs was assessed by means of real-time PCR in fresh nasal epithelial cell scrapings obtained before and daily up to 4 days after infection.
dsRNA exposure of BEAS2B and human primary bronchial epithelial cells resulted in increased levels of cell-surface and mRNA expression of B7-H1 and B7-DC but not B7-H2 or B7-H3. Exposure of primary cells to HRV-16 resulted in induction of cell-surface expression of B7-H1 and B7-DC. Pretreatment with fluticasone propionate failed to suppress the induction of B7-H1 and B7-DC. Nasal scrapings taken at the time of peak symptom scores (3 days) after infection of 6 human subjects with HRV-16 displayed selective induction of levels of mRNA for B7-H1 and B7-DC.
These data show that HRV-16 infection or exposure to dsRNA induces epithelial B7-H1 and B7-DC.
上皮组织中的T细胞浸润是慢性鼻-鼻窦炎和哮喘的关键特征。病毒感染是疾病加重的重要原因。我们发现病毒可诱导气道上皮细胞表达与T细胞相互作用的配体,即B7同源共刺激分子。
我们测试了人鼻病毒16型(HRV)和双链RNA(dsRNA)改变人气道上皮细胞上B7同源分子表达的能力。
将BEAS2B细胞和原代人气道上皮细胞在体外暴露于dsRNA(25μg/mL)或HRV-16,然后分别通过流式细胞术和实时PCR评估B7同源分子的细胞表面蛋白表达和mRNA表达。此外,在体内用人感染HRV-16,并通过实时PCR在感染前及感染后直至第4天每天采集的新鲜鼻上皮细胞刮片中评估B7同源分子的mRNA。
BEAS2B细胞和人原代支气管上皮细胞暴露于dsRNA后,B7-H1和B7-DC的细胞表面表达水平及mRNA表达水平升高,但B7-H2或B7-H3未升高。原代细胞暴露于HRV-16后,可诱导B7-H1和B7-DC的细胞表面表达。丙酸氟替卡松预处理未能抑制B7-H1和B7-DC的诱导。6名感染HRV-16的人类受试者在症状评分峰值(3天)时采集的鼻刮片显示,B7-H1和B7-DC的mRNA水平有选择性诱导。
这些数据表明,HRV-16感染或暴露于dsRNA可诱导上皮细胞表达B7-Hl和B7-DC。