Pathogenesis and treatment of common cold-induced exacerbations of bronchial asthma

1. 为了研究低密度脂蛋白（LDL）受体在人鼻病毒小亚群感染中的作用，我们培养了人气管上皮细胞。将人鼻病毒2型（RV2）释放到上清液中，RV2感染可调节上清液中白细胞介素(IL)- β、IL-6、IL-8和肿瘤坏死因子(TNF)- α的产生。ldl受体抗体抑制RV2感染，降低RV2感染后细胞因子的产生。此外，RV2感染可调节ldl受体mRNA的表达。这些发现表明鼻病毒亚群可以通过细胞上的低密度脂蛋白受体感染人气道上皮细胞。2. 为了研究鼻病毒感染是否会损害上皮屏障功能，我们将人鼻病毒14型（RV14）感染到人气管上皮细胞培养物中。过氧化氢（H_2O_<>）增加了Ussing's chamber法测量的上皮细胞片上的电导率(G)。在il -1 β预处理条件下，RV14感染增强了H_2O_<>-诱导的G和[^3H]-甘露醇通过培养上皮通量的增加。il -1 β增强细胞间粘附分子-1 （icam -1）的表达。这些发现表明，RV14可能通过上调icam -1 β来降低气道上皮的屏障功能。我们检测了地塞米松、红霉素和H’atpase抑制剂巴霉素对上清液中RVl4释放和细胞因子含量的影响，发现这些处理降低了上清液的病毒升和上清液中il -1 β、IL-6、IL-8和tnf - α细胞因子的产生。这些治疗可以抑制鼻病毒感染，调节由鼻病毒感染引起的气道炎症。

1. To examine the role of the low density lipoprotein (LDL) receptor on the infection of minor subgroup human rhinovirus, we cultured human tracheal epithelial cells. Human rhinovirus type 2 (RV2) was released into supernatants, and RV2 infection unregulated the production of interleukin (IL)-lbeta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha in supernatants. Antibodies to the LDLreceptor inhibited RV2 infection and decreased the production of cytokines after RV2 infection. Furthermore, RV2 infection unregulated LDLreceptor mRNA expression. These finding suggest that minor subgroup rhinovirus can infect human airway epithelial cells via a LDL receptor on the cells. 2. To examine whether rhinovirus infection impairs epithelial barrier functions, human rhinovirus type 14(RV14) was infected to cultures of human tracheal epithelial cells. Hydrogen peroxide (H_2O_<>) increased electrical conductance (G) across the epithelial cell sheet measured with Ussing's chamber methods. RV14 infection potentiated H_2O_<>-induced increases in G and [^3H]-mannitol flux through the cultured epithelium in IL-1beta pretreated conditions. IL-1beta enhanced intercellular adhesion molecule-l (ICAM-l) expression. These findings suggest that RV14 may reduce barrier functions in the airway epithelium in association with upregulation of ICAM-1beta. We examined the effects of dexamethasone, erythromycin and H'ATPase inhibitor bafilomycin on RVl4 release and cytokine content in the supernatants, and found that these treatment reduced virus Liter of supernatants and cytokines production of IL-1beta, IL-6, IL-8 and TNF-alpha in supernatants. These treatment may inhibit rhinovirus infection and modulate airway inflammation caused by rhinovirus infection.