Tumor necrosis factor-α -: Induced synthesis of interleukin-16 in airway epithelial cells -: Priming for serotonin stimulation
Tumor necrosis factor-α -: Induced synthesis of interleukin-16 in airway epithelial cells -: Priming for serotonin stimulation
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DOI：
10.1165/rcmb.2002-0043oc
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发表时间：
2003-03-01
影响因子：
6.4
通讯作者：
Cruikshank, WW
中科院分区：
文献类型：
--
作者：
Little, FF;Lynch, E;Cruikshank, WW
来自哮喘个体或过敏原致敏小鼠的上皮细胞含有细胞内白细胞介素(IL)-16蛋白，而非哮喘个体或未致敏小鼠的上皮细胞中不存在这种蛋白。IL-16仅存在于支气管肺泡灌洗液（BAL）后气道挑战过敏原或血管活性胺。这表明对过敏原的初始反应（致敏）导致了IL-16的合成而不是分泌。在这项研究中，我们研究了敏化阶段产生的哪些因子负责上皮细胞启动IL-16的产生。我们确定卵清蛋白（OVA）致敏小鼠全身肿瘤坏死因子- α水平增加，并且支气管上皮细胞的血清或BAL液刺激导致IL-16的产生，该IL-16随后仅在5 -羟色胺刺激后分泌。IL-16的产生机制是caspase-3依赖性的，血清素诱导IL-16的分泌需要与血清素2型受体结合。在ova致敏小鼠的体内实验中，5 -羟色胺气道刺激导致IL-16快速分泌到BAL液中，证实了与致敏相关的启动效应与IL-16产生和储存的相关性。由于IL-16已被证明可以调节CD4+细胞的募集和激活，并且在哮喘患者气道攻击后早期被检测到，上皮细胞产生IL-16的这两步过程可能代表了过敏性气道炎症的快速反应机制。
Epithelial cells from individuals with asthma or from allergen-sensitized mice contain intracellular interleukin (IL)-16 protein, not present in epithelial cells from individuals without asthma or unsensitized mice. IL-16 is only present in the bronchoalveolar lavage (BAL) fluid following airway challenge with either allergen or vasoactive amine. This suggests that the initial response to allergen (sensitization) results in synthesis but not secretion of IL-16. In this study, we investigated what factors produced during the sensitization phase are responsible for epithelial cell priming for IL-16 production. We determined that ovalbumin (OVA)-sensitized mice have an increase in systemic tumor necrosis factor-alpha levels, and that serum or BAL fluid stimulation of bronchial epithelial cells results in production of IL-16 that is subsequently secreted only following serotonin stimulation. The mechanism for IL-16 production was shown to be caspase-3-dependent, and serotonin-induced secretion of IL-16 required binding of the serotonin type 2 receptor. The relevance of the priming effect associated with sensitization for IL-16 production and storage was confirmed in vivo by serotonin airway challenge of OVA-sensitized mice, resulting in rapid secretion of IL-16 into BAL fluid. As IL-16 has been shown to regulate CD4+ cell recruitment and activation, and is detected early following airway challenge of individuals with asthma, this two-step process for IL-16 production by epithelial cells may represent a rapid response mechanism in the orchestration of allergic airway inflammation.