Studies on the mechanisms of cold-induced bronchial asthma

支气管哮喘的加重常与鼻病毒感染引起的呼吸道感染有关。为了研究鼻病毒对呼吸道病毒的主要靶点——呼吸道上皮的感染，我们将人鼻病毒14 （HRV-14）感染到人气管上皮培养物中。病毒感染被证实，显示病毒滴度随时间增加的上清液。感染HRV-14后，上清液中il -1 β、IL-6、IL-8和tnf - α的表达增加，细胞间黏附分子-1 (ICAM-1) mRNA表达上调。血红素上调上皮细胞血红素加氧酶1 (HO-1) mRNA表达，降低上清液病毒滴度。然后用HO-1特异性抑制剂SnPP9 （Sn protoporphyrin IX, SnPP9）提高上清液中降低的病毒滴度。人气管粘膜下腺培养物感染HRV-14后，其上清液HRV-14滴度随时间增加而升高。HRV-14上调人气管粘膜下腺ICAM-1、il -1 β、IL-6、IL-8、tnf - α和GM-CSF的表达。这些结果提示，鼻病毒感染后气道上皮细胞和粘膜下腺细胞细胞因子和ICAM-1产生的上调可能与气道炎症有关，HO-1可能对鼻病毒感染具有保护作用。

Exacerbations of bronchial asthma are often associated with respiratory infection caused by rhinovirus infection. To examine the rhinovirus infection on respiratory epithelium, a primary target for respiratory viruses, human rhinovirus 14 (HRV-14) was infected to cultures from the human tracheal epithelium. Viral infection was confirmed by showing that viral titers of supernatants infcreased with time. HRV-14 infection up-regulated the intercellular adhesion molecule-1 (ICAM-1) mRNA,the receptor for the virus, on epithelial cells and it increased the production of IL-1beta, IL-6, IL-8 and TNF-alpha in supernatants. Hemin up-regulated the heme oxygenase 1 (HO-1) mRNA expression on epithelial cells and reduced the viral titers of supernatants. The decreased viral titers of supernatants were then increased by Sn protoporphyrin IX (SnPP9), a specific inhibitor for HO-1. Furthermore, HRV-14 was infected to cultures of human tracheal submucosal glands and HRV-14 titers of supernatants increased with time. HRV-14 up-regulated production of ICAM-1 and IL-1beta, IL-6, IL-8, TNF-alpha and GM-CSF by the cultured human tracheal submucosal glands. These results suggest that up-regulation of cytokines and ICAM-1 production by the cells of airway epithelium and submucosal glands may relate to airway inflammation after rhinovirus infection, and that HO-1 may have a protective effect against rhinovirus infection.