PDF(Pubmed)
Abstract：
Histamine-releasing factor (HRF) is a multifunctional protein with fundamental intracellular functions controlling cell survival and proliferation. HRF is also secreted during allergic reactions and promotes IgE-mediated activation of mast cells and basophils. In this study, we investigated HRF secretion and its relevance to airway inflammation. HRF monomers were constitutively secreted from BEAS-2B human bronchial epithelial cells (HBECs) and converted to oligomers over the course of culture. Stimulation with house dust mite (HDM) extract increased HRF secretion substantially. Several cytokines involved in asthma pathogenesis showed moderate effects on HRF secretion but dramatically enhanced HDM-induced HRF secretion. HDM-induced HRF secretion from BEAS-2B cells and normal HBECs proceeded via TLR2. Consistent with this, multiple TLR2 ligands, including Der p 2, Der p 5, Der p 13, and Der p 21, induced HRF secretion. Der p 10 (tropomyosin) also promoted HRF secretion. Cell death or incubation with adenosine and ATP, compounds released upon cell death, also enhanced HRF secretion. Furthermore, intranasal administration of recombinant HRF elicited robust airway inflammation in HDM-sensitized mice in an FcεRI-dependent manner. Therefore, we conclude that HRF is a novel alarmin that promotes allergic airway inflammation.
摘要：
组胺释放因子（HRF）是一种多功能蛋白，具有控制细胞存活和增殖的基本细胞内功能。HRF也在过敏反应期间分泌,并促进IgE介导的肥大细胞和嗜碱性粒细胞的活化。在这项研究中,我们研究了HRF分泌及其与气道炎症的相关性。HRF单体由BEAS-2B人支气管上皮细胞（HBEC）组成型分泌，并在培养过程中转化为寡聚体。用屋尘螨（HDM）提取物刺激可大大增加HRF的分泌。与哮喘发病机制有关的几种细胞因子对HRF分泌有中等影响，但显着增强了HDM诱导的HRF分泌。HDM诱导的BEAS-2B细胞和正常HBEC的HRF分泌通过TLR2进行。与此一致，多个TLR2配体，包括Derp2、Derp5、Derp13和Derp21，诱导HRF分泌。Derp10（原肌球蛋白）也促进HRF分泌。细胞死亡或与腺苷和ATP孵育，细胞死亡时释放的化合物，也增强了HRF的分泌。此外，鼻内施用重组HRF以FcεRI依赖性方式在HDM致敏小鼠中引起强烈的气道炎症。因此,我们得出的结论是,HRF是一种新型的alarmin,可促进过敏性气道炎症.
