Hakonarson H, Carter C, Maskeri N, Hodinka R, Grunstein M M
Division of Pulmonary Medicine, Joseph Stokes, Jr. Research Institute, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Am J Physiol. 1999 Jul;277(1):L13-21. doi: 10.1152/ajplung.1999.277.1.L13.
An important interplay exists between specific viral respiratory pathogens, most commonly rhinovirus (RV), and altered airway responsiveness in the development and exacerbations of asthma. Given that RV infection reportedly induces the release of various cytokines in different cell types and that the reported effects of RV on airway smooth muscle (ASM) responsiveness are highly comparable to those obtained in ASM exposed to the proinflammatory cytokine interleukin (IL)-1beta, this study examined whether RV (serotype 16)-mediated pertubations in ASM responsiveness are mechanistically coupled to altered induced expression and action of IL-1beta in RV-exposed isolated rabbit and human ASM tissue and cultured cells. Relative to control tissues, ASM inoculated with RV exhibited significantly increased maximal isometric contractility to ACh (P < 0.01) and attenuated relaxation to isoproterenol (P < 0. 005). In extended studies, we found that 1) the RV-induced changes in ASM responsiveness were ablated by pretreating the tissues with the IL-1 recombinant human receptor antagonist; 2) in contrast to their respective controls, RV-inoculated ASM tissue and cultured cells exhibited progressively induced expression of IL-1beta mRNA and elaboration of IL-1beta protein at 6 and 24 h after viral exposure; and 3) the latter effect of RV was inhibited in the presence of a monoclonal antibody to intercellular adhesion molecule-1, the endogenous receptor for most RV. Collectively, these observations provide new evidence demonstrating that "pro-asthmatic-like" pertubations in agonist responsiveness elicited in RV-exposed ASM are largely attributed to the induced autologous expression and autocrine action of IL-1beta in the virus-infected ASM.
在特定的病毒性呼吸道病原体（最常见的是鼻病毒（RV））与哮喘发展和加重过程中气道反应性改变之间，存在着重要的相互作用。鉴于据报道RV感染可诱导不同细胞类型释放多种细胞因子，且据报道RV对气道平滑肌（ASM）反应性的影响与暴露于促炎细胞因子白细胞介素（IL）-1β的ASM所获得的影响高度相似，本研究探讨了RV（16型）介导的ASM反应性扰动在机制上是否与RV暴露的离体兔和人ASM组织及培养细胞中IL-1β诱导表达和作用的改变相关。与对照组织相比，接种RV的ASM对乙酰胆碱（ACh）的最大等长收缩力显著增加（P < 0.01），对异丙肾上腺素的舒张反应减弱（P < 0.005）。在进一步的研究中，我们发现：1）用IL-1重组人受体拮抗剂预处理组织可消除RV诱导的ASM反应性变化；2）与各自的对照相比，接种RV的ASM组织和培养细胞在病毒暴露后6小时和24小时表现出IL-1β mRNA的逐渐诱导表达和IL-1β蛋白的分泌；3）在存在针对细胞间黏附分子-1（大多数RV的内源性受体）的单克隆抗体的情况下，RV的后一种作用受到抑制。总的来说，这些观察结果提供了新的证据，表明在暴露于RV的ASM中引发的激动剂反应性“类哮喘样”扰动很大程度上归因于病毒感染的ASM中IL-1β的诱导自分泌表达和自分泌作用。
