Ty-Jour T1 - 肺铁水平和调节在哮喘发病机制和严重程度的关键作用 - 欧洲呼吸杂志Jo - Eur Respir J Do - 10.11.01340-2019 VL - 55 IS - 4 SP - 1901340 Au - Ali，MD。Khadem Au - Kim，Richard Y. Au-Brown，Alexandra C. Au - Mayall，Jemma R. Au - Karim，Rafia Au - Pinkerton，James W. Au - Liu，Gang Au - Martin，Kristy L. Au -STARKEY，MATCOLM R. AU - Parkar，Amber L. Au - Donovan，Chantal Au - Pathinayake，Prabuddha S. Au - Carroll，Olivia R. Au - Trinder，Debbie Au - Tay，Hock L. Au - Badi，Yusef E.Au - Kermani，Nazanin Z. Au - Guo，Yi-ke Au - aryal，Ritambhara Au - Mumby，Sharon Au - Pavlidis，Stelios Au - Adcock，Ian M. Au - Weaver，Jessica Au - Xenaki，Dikaia Au - Oliver，Brian G. Au - Holliday，Elizabeth G. Au - Foster，Paul S. Au - Wark，Peter A. Au - Johnstone，Daniel M. Au - 米兰，Elizabeth A. Au - Hansbro，Philip M. Au - Horvat，Jay，JayC. Y1 - 2020 / 04/01 UR - //www.qdcxjkg.com/content/55/4/1901340.abstRACT N2 - 累积证据突出了铁调控与呼吸系统疾病之间的联系。在这里，我们评估了临床和实验性哮喘中的铁水平与调节反应之间的关系。我们表明，严重或轻度中度哮喘患者的支气管肺泡灌洗（BAL）上清液中，无细胞的铁水平降低，与较低的强制呼气相关1 s中的卷（fev1）。相反，这些患者的BAL中载有熨斗的细胞数量增加，并且具有较低的FEV1 /强制致命能力（FVC）比率。 The airway tissue expression of the iron sequestration molecules divalent metal transporter 1 (DMT1) and transferrin receptor 1 (TFR1) are increased in asthma, with TFR1 expression correlating with reduced lung function and increased Type-2 (T2) inflammatory responses in the airways. Furthermore, pulmonary iron levels are increased in a house dust mite (HDM)-induced model of experimental asthma in association with augmented Tfr1 expression in airway tissue, similar to human disease. We show that macrophages are the predominant source of increased Tfr1 and Tfr1+ macrophages have increased Il13 expression. We also show that increased iron levels induce increased pro-inflammatory cytokine and/or extracellular matrix (ECM) responses in human airway smooth muscle (ASM) cells and fibroblasts ex vivo and induce key features of asthma in vivo, including airway hyper-responsiveness (AHR) and fibrosis, and T2 inflammatory responses.Together these complementary clinical and experimental data highlight the importance of altered pulmonary iron levels and regulation in asthma, and the need for a greater focus on the role and potential therapeutic targeting of iron in the pathogenesis and severity of disease.The relationship between iron and the pathogenesis of asthma remains unclear. Here it is shown for the first time that altered iron responses are a key feature of clinical and experimental asthma and may play important roles in disease. http://bit.ly/36JKajt ER -