胰岛素样生长因子结合蛋白-3在变应性气道重塑中的作用
2010/01/07
气道炎症、阻塞和重塑是变应性哮喘的特征，气道重塑会导致不可逆性气流受阻从而提高哮喘的发病率和病死率。胰岛素样生长因子结合蛋白（IGFBPs）已被报道有利于特发性肺纤维化中细胞外基质沉积，而其在哮喘气道重塑中的作用还未明确。作者通过蛋白印迹法、酶联免疫吸附测定及免疫荧光法，分别测定IGFBP-3在哮喘患者基线及过敏原激发后48小时组织和BALF中的水平。
结果发现：哮喘患者气道上皮细胞及经抗原激发后BALF中IGFBP-3表达升高；体外修复上皮细胞和IGF-1刺激后的原发上皮细胞培养的基质中IGFBP-3表达均增加。结论：变应性气道重塑机制之一是通过IGF-1刺激后气道上皮细胞分泌促纤维化的IGFBP-3实现的。
（农英 卫生部中日友好医院呼吸内科 100029 摘译）
（Am J Respir Crit Care Med. 2009 Oct 1;180(7):611-617）
Role of insulin-like growth factor binding protein-3 in allergic airway remodeling.
Veraldi KL, Gibson BT, Yasuoka H, Myerburg MM, Kelly EA, Balzar S, Jarjour NN, Pilewski JM, Wenzel SE, Feghali-Bostwick CA.
RATIONALE: The hallmarks of allergic asthma are airway inflammation, obstruction, and remodeling. Airway remodeling may lead to irreversible airflow obstruction with increased morbidity and mortality. Despite advances in the treatment of asthma, the mechanisms underlying airway remodeling are still poorly understood. We reported that insulin-like growth factor (IGF) binding proteins (IGFBPs) contribute to extracellular matrix deposition in idiopathic pulmonary fibrosis; however, their contribution to airway remodeling in asthma has not been established.
OBJECTIVES: We hypothesized that IGFBP-3 is overexpressed in asthma and contributes to airway remodeling.
METHODS: We evaluated levels of IGFBP-3 in tissues and bronchoalveolar lavage fluid from patients with asthma at baseline and 48 hours after allergen challenge, in reparative epithelium in an in vitro wounding assay, and in conditioned media from cytokine- and growth factor-stimulated primary epithelial cells.
MEASUREMENTS AND MAIN RESULTS: IGFBP-3 levels and distribution were evaluated by Western blot, ELISA, and immunofluorescence. IGFBP-3 is increased in vivo in the airway epithelium of patients with asthma compared with normal control subjects. The concentration of IGFBP-3 is increased in the bronchoalveolar lavage fluid of patients with asthma after allergen challenge, its levels are increased in reparative epithelium in an in vitro wounding assay and in the conditioned medium of primary airway epithelial cell cultures stimulated with IGF-I.
CONCLUSIONS: Our results suggest that one mechanism of allergic airway remodeling is through the secretion of the profibrotic IGFBP-3 from IGF-I-stimulated airway epithelial cells during allergic inflammation.
Am J Respir Crit Care Med. 2009 Oct 1;180(7):611-7
结果发现：哮喘患者气道上皮细胞及经抗原激发后BALF中IGFBP-3表达升高；体外修复上皮细胞和IGF-1刺激后的原发上皮细胞培养的基质中IGFBP-3表达均增加。结论：变应性气道重塑机制之一是通过IGF-1刺激后气道上皮细胞分泌促纤维化的IGFBP-3实现的。
（农英 卫生部中日友好医院呼吸内科 100029 摘译）
（Am J Respir Crit Care Med. 2009 Oct 1;180(7):611-617）
Role of insulin-like growth factor binding protein-3 in allergic airway remodeling.
Veraldi KL, Gibson BT, Yasuoka H, Myerburg MM, Kelly EA, Balzar S, Jarjour NN, Pilewski JM, Wenzel SE, Feghali-Bostwick CA.
RATIONALE: The hallmarks of allergic asthma are airway inflammation, obstruction, and remodeling. Airway remodeling may lead to irreversible airflow obstruction with increased morbidity and mortality. Despite advances in the treatment of asthma, the mechanisms underlying airway remodeling are still poorly understood. We reported that insulin-like growth factor (IGF) binding proteins (IGFBPs) contribute to extracellular matrix deposition in idiopathic pulmonary fibrosis; however, their contribution to airway remodeling in asthma has not been established.
OBJECTIVES: We hypothesized that IGFBP-3 is overexpressed in asthma and contributes to airway remodeling.
METHODS: We evaluated levels of IGFBP-3 in tissues and bronchoalveolar lavage fluid from patients with asthma at baseline and 48 hours after allergen challenge, in reparative epithelium in an in vitro wounding assay, and in conditioned media from cytokine- and growth factor-stimulated primary epithelial cells.
MEASUREMENTS AND MAIN RESULTS: IGFBP-3 levels and distribution were evaluated by Western blot, ELISA, and immunofluorescence. IGFBP-3 is increased in vivo in the airway epithelium of patients with asthma compared with normal control subjects. The concentration of IGFBP-3 is increased in the bronchoalveolar lavage fluid of patients with asthma after allergen challenge, its levels are increased in reparative epithelium in an in vitro wounding assay and in the conditioned medium of primary airway epithelial cell cultures stimulated with IGF-I.
CONCLUSIONS: Our results suggest that one mechanism of allergic airway remodeling is through the secretion of the profibrotic IGFBP-3 from IGF-I-stimulated airway epithelial cells during allergic inflammation.
Am J Respir Crit Care Med. 2009 Oct 1;180(7):611-7
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阿奇霉素可以减轻过敏性哮喘模型小鼠非感染性气道炎症
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VRGF多态性和儿童哮喘、肺功能和气道反应性的关系
