Studies on the mechanisms of cold-induced bronchial asthma

支气管哮喘的急性发作常与鼻病毒感染引起的呼吸道感染有关。为了检测鼻病毒对呼吸道上皮（呼吸道病毒的主要靶标）的感染，将人鼻病毒14（HRV-14）感染至来自人气管上皮的培养物。通过显示上清液的病毒滴度随时间增加来证实病毒感染。HRV-14感染上调了上皮细胞上的细胞间粘附分子-1（ICAM-1）mRNA（病毒的受体），并增加了上清液中IL-1 β、IL-6、IL-8和TNF-α的产生。氯化血红素可上调上皮细胞血红素氧合酶1（HO-1）mRNA的表达，降低病毒滴度。然后通过Sn原卟啉IX（SnPP 9）（HO-1的特异性抑制剂）增加上清液的降低的病毒滴度。此外，HRV-14感染人气管粘膜下腺培养物，上清液中HRV-14滴度随时间增加。HRV-14可上调培养的人气管粘膜下腺体ICAM-1和IL-1 β、IL-6、IL-8、TNF-α和GM-CSF的产生。这些结果提示，鼻病毒感染后气道上皮细胞和粘膜下腺体细胞产生细胞因子和ICAM-1的上调可能与气道炎症有关，HO-1可能具有抗鼻病毒感染的保护作用。

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.