Yoneda Kazuo, Rokutan Kazuhito, Nakamura Yoichi, Yanagawa Hiroaki, Kondo-Teshima Shigetada, Sone Saburo
Department of Internal Medicine and Molecular Therapeutics, University of Tokushima School of Medicine, Kuramoto-cho 3, Tokushima 770-8503, Japan.
Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L174-81. doi: 10.1152/ajplung.00118.2003. Epub 2003 Aug 29.
An IgE-dependent histamine-releasing factor (HRF p23; also known as translationally controlled tumor protein or p23) stimulates the release of histamine, IL-4, and IL-13 from a subpopulation of highly allergic donor basophils. It has also been shown to act as a chemoattractant for eosinophils. To elucidate novel functions of HRF p23 in airway inflammation, we examined the effects of human recombinant HRF p23 (hrHRF) on bronchial epithelium and found that hrHRF stimulated the secretions of IL-8 and granulocyte/macrophage colony-stimulating factor by both primary cultures of human bronchial epithelial cells and BEAS-2B cells. In response to hrHRF, these cells induced IL-8 mRNA expression within 4 h. H2O2, but not IL-1 beta or tumor necrosis factor-alpha, stimulated secretion of HRF p23 by BEAS-2B cells, suggesting that oxidative stress may trigger the release of HRF p23 from bronchial epithelial cells. Bronchoalveolar lavage (BAL) from healthy volunteers contained only trivial or undetectable amounts of HRF p23. Significantly higher amounts of HRF p23 were recovered from BAL fluid taken from asthmatic patients, and the amounts of HRF p23 were further elevated in patients with idiopathic eosinophilic pneumonia. Our results demonstrate for the first time that HRF p23 can stimulate nonimmune epithelium. HRF p23 derived from bronchial epithelial cells may regulate complex cytokine networks in eosinophil-dependent inflammation of the human airway.
一种依赖IgE的组胺释放因子（HRF p23；也称为翻译调控肿瘤蛋白或p23）可刺激高度过敏供体嗜碱性粒细胞亚群释放组胺、白细胞介素-4和白细胞介素-13。它还被证明可作为嗜酸性粒细胞的趋化因子。为了阐明HRF p23在气道炎症中的新功能，我们检测了人重组HRF p23（hrHRF）对支气管上皮的影响，发现hrHRF可刺激人支气管上皮细胞原代培养物和BEAS-2B细胞分泌白细胞介素-8和粒细胞/巨噬细胞集落刺激因子。响应hrHRF，这些细胞在4小时内诱导白细胞介素-8 mRNA表达。过氧化氢而非白细胞介素-1β或肿瘤坏死因子-α刺激BEAS-2B细胞分泌HRF p23，提示氧化应激可能触发支气管上皮细胞释放HRF p23。健康志愿者的支气管肺泡灌洗（BAL）液中仅含有微量或无法检测到的HRF p23。从哮喘患者的BAL液中回收的HRF p23量显著更高，而特发性嗜酸性粒细胞性肺炎患者的HRF p23量进一步升高。我们的结果首次证明HRF p23可刺激非免疫性上皮细胞。源自支气管上皮细胞的HRF p23可能在人类气道嗜酸性粒细胞依赖性炎症中调节复杂的细胞因子网络。
