关键词: airway hyperresponsiveness airway inflammation asthma particulate β‐glucans (WGP)

Mesh : Animals Asthma / immunology drug therapy pathology Mast Cells / immunology drug effects metabolism Mice Disease Models, Animal Administration, Oral Mice, Inbred C57BL beta-Glucans / pharmacology administration & dosage Cytokines / metabolism Inflammation / drug therapy immunology Ovalbumin / immunology Respiratory Hypersensitivity / drug therapy immunology Bronchoalveolar Lavage Fluid / immunology Lung / immunology pathology drug effects

来  源:   DOI:10.1002/iid3.1333   PDF(Pubmed)

Abstract:
BACKGROUND: Particulate β-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown.
METHODS: C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF).
RESULTS: The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF.
CONCLUSIONS: These results highlight OAW\'s robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.
摘要:
背景:颗粒β-葡聚糖(WGP)是在各种生物过程中具有调节作用的天然化合物,包括肿瘤发生和炎症性疾病,如过敏性哮喘。然而,它们对肥大细胞(MC)的影响,哮喘小鼠气道高反应性(AHR)和炎症的贡献者,仍然未知。
方法:C57BL/6小鼠在没有明矾的情况下反复进行OVA致敏,其次是卵清蛋白(OVA)挑战。小鼠在致敏和攻击前每天口服50或150mg/kg剂量的WGP(OAW)。我们评估了气道功能,肺组织病理学,气道中的肺部炎症细胞成分,以及支气管肺泡灌洗液(BALF)中的促炎细胞因子和趋化因子。
结果:150mg/kgOAW治疗减轻了OVA诱导的AHR和气道炎症,气道对雾化乙酰甲胆碱(Mch)的反应性降低证明,炎性细胞浸润减少,肺组织杯状细胞增生。此外,OAW阻碍了炎症细胞的募集,包括MC和嗜酸性粒细胞,在肺组织和BALF中。OAW治疗可减弱BALF中的促炎性肿瘤坏死因子(TNF)-α和IL-6水平。值得注意的是,OAW显著下调趋化因子CCL3、CCL5、CCL20、CCL22、CXCL9和CXCL10在BALF中的表达。
结论:这些结果突出了OAW的强大抗炎特性,提示通过影响炎症细胞浸润和调节气道中的促炎细胞因子和趋化因子治疗MC依赖性AHR和过敏性炎症的潜在益处。
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