有氧运动对哮喘分子方面的影响：SOCS-JAK-STAT的参与
2019/03/21
摘要
背景：有氧训练（AT）减少哮喘的气道炎症，但潜在的细胞和分子机制尚不完全清楚。因此，该研究评估了SOCS-JAK-STAT信号通路在AT对过敏性气道炎症模型中气道炎症，重塑和高反应性的影响。
方法：将C57Bl / 6小鼠分成对照组（Co），训练组（Ex），HDM组（HDM）和HDM +训练组（HDM + Ex）。在第0,7,14,21,28,35,42和49天经口气管给予粉尘螨（100ug /小鼠）。从第24天至第52天的4周内，让小鼠在跑步机上进行中等强度的AT 。
结果：AT降低HDM诱导的BAL中总细胞（p <0.001），嗜酸性粒细胞（p <0.01），中性粒细胞（p <0.01）和淋巴细胞（p <0.01）以及支气管周围嗜酸性粒细胞（p <0.01），中性粒细胞（p <0.01）和淋巴细胞（p <0.01）的数量。 AT还降低BAL中IL-4（p <0.001），IL-5（p <0.001），IL-13（p <0.001），CXCL1（p <0.01），IL-17（p <0.01），IL-23（p <0.05），IL-33（p <0.05）的表达水平，同时增加IL-10的表达水平（p <0.05）。 AT引起气道胶原纤维（p <0.01），弹性纤维p <0.01）和粘蛋白（p <0.01）的量减少。 AT抑制了HDM诱导的气道对乙酰甲胆碱6,25mg / ml（p <0.01），12.5mg / mL（p <0.01），25mg / mL（p <0.01）和50mg / mL（p < 0.01）的高反应性（AHR）。另外，AT降低支气管周围白细胞和气道上皮细胞STAT6（p <0.05），STAT3（p <0.001），STAT5（p <0.01）和JAK2（p <0.001）的表达，同时上调白细胞和气道上皮细胞 SOCS1表达（p <0.001），上调白细胞SOCS2表达（p <0.01），下调白细胞和气道上皮细胞SOCS3表达（p <0.001）。
结论：AT降低了SOCSJAK-STAT信号通路参与的哮喘表型。
Effects of aerobic exercise on molecular aspects of asthma: involvement of SOCS-JAK-STAT.
Almeida-Oliveira AR, Aquino-Junior J, Abbasi A, Santos-Dias A, Oliveira-Junior MC, Alberca-Custodio RW, Rigonato-Oliveira NC, Salles-Dias LP, Damaceno-Rodrigues NR, Caldini EG, Arantes-Costa FM, Ligeiro-Oliveira AP, Belvisi MG, Vieira RP.
Abstract
BACKGROUND:Aerobic training (AT) decreases airway inflammation in asthma, but the underlying cellular and molecular mechanisms are not completely understood. Thus, this study evaluated the participation of SOCS-JAK-STAT signaling in the effects of AT on airway inflammation, remodeling and hyperresponsiveness in a model of allergic airway inflammation.
METHODS:C57Bl/6 mice were divided into Control (Co), Exercise (Ex), HDM (HDM), and HDM+Exercise (HDM+ Ex). Dermatophagoides pteronyssinus (100ug/mouse) were administered oro-tracheally on days 0, 7, 14, 21, 28, 35, 42 and 49. AT was performed in a treadmill during 4 weeks in moderate intensity, from day 24 until day 52.
RESULTS:AT inhibited HDM-induced total cells (p<0.001), eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in BAL, and eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in peribronchial space. AT also reduced BAL levels of IL-4 (p<0.001), IL-5 (p<0.001), IL-13 (p<0.001), CXCL1 (p<0.01), IL-17 (p<0.01), IL-23 (p<0.05), IL-33 (p<0.05), while increased IL- 10 (p<0.05). Airway collagen fibers (p<0.01), elastic fibers p<0.01) and mucin (p<0.01) were also reduced by AT. AT also inhibited HDM-induced airway hyperresponsiveness (AHR) to methacholine 6,25mg/ml (p<0.01), 12,5mg/mL (p<0.01), 25mg/mL (p<0.01) and 50mg/mL (p<0.01). Mechanistically, AT reduced the expression of STAT6 (p<0.05), STAT3 (p<0.001), STAT5 (p<0.01) and JAK2 (p<0.001), similarly by peribronchial leukocytes and by airway epithelial cells. SOCS1 expression (p<0.001) was upregulated in leukocytes and in epithelial cells, SOCS2 (p<0.01) was upregulated in leukocytes and SOCS3 down-regulated in leukocytes (p<0.05) and in epithelial cells (p<0.001).
CONCLUSIONS:AT reduces asthma phenotype involving SOCSJAK- STAT signaling.
背景：有氧训练（AT）减少哮喘的气道炎症，但潜在的细胞和分子机制尚不完全清楚。因此，该研究评估了SOCS-JAK-STAT信号通路在AT对过敏性气道炎症模型中气道炎症，重塑和高反应性的影响。
方法：将C57Bl / 6小鼠分成对照组（Co），训练组（Ex），HDM组（HDM）和HDM +训练组（HDM + Ex）。在第0,7,14,21,28,35,42和49天经口气管给予粉尘螨（100ug /小鼠）。从第24天至第52天的4周内，让小鼠在跑步机上进行中等强度的AT 。
结果：AT降低HDM诱导的BAL中总细胞（p <0.001），嗜酸性粒细胞（p <0.01），中性粒细胞（p <0.01）和淋巴细胞（p <0.01）以及支气管周围嗜酸性粒细胞（p <0.01），中性粒细胞（p <0.01）和淋巴细胞（p <0.01）的数量。 AT还降低BAL中IL-4（p <0.001），IL-5（p <0.001），IL-13（p <0.001），CXCL1（p <0.01），IL-17（p <0.01），IL-23（p <0.05），IL-33（p <0.05）的表达水平，同时增加IL-10的表达水平（p <0.05）。 AT引起气道胶原纤维（p <0.01），弹性纤维p <0.01）和粘蛋白（p <0.01）的量减少。 AT抑制了HDM诱导的气道对乙酰甲胆碱6,25mg / ml（p <0.01），12.5mg / mL（p <0.01），25mg / mL（p <0.01）和50mg / mL（p < 0.01）的高反应性（AHR）。另外，AT降低支气管周围白细胞和气道上皮细胞STAT6（p <0.05），STAT3（p <0.001），STAT5（p <0.01）和JAK2（p <0.001）的表达，同时上调白细胞和气道上皮细胞 SOCS1表达（p <0.001），上调白细胞SOCS2表达（p <0.01），下调白细胞和气道上皮细胞SOCS3表达（p <0.001）。
结论：AT降低了SOCSJAK-STAT信号通路参与的哮喘表型。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(Exerc Immunol Rev. 2019;25:50-62. )
(Exerc Immunol Rev. 2019;25:50-62. )
Effects of aerobic exercise on molecular aspects of asthma: involvement of SOCS-JAK-STAT.
Almeida-Oliveira AR, Aquino-Junior J, Abbasi A, Santos-Dias A, Oliveira-Junior MC, Alberca-Custodio RW, Rigonato-Oliveira NC, Salles-Dias LP, Damaceno-Rodrigues NR, Caldini EG, Arantes-Costa FM, Ligeiro-Oliveira AP, Belvisi MG, Vieira RP.
Abstract
BACKGROUND:Aerobic training (AT) decreases airway inflammation in asthma, but the underlying cellular and molecular mechanisms are not completely understood. Thus, this study evaluated the participation of SOCS-JAK-STAT signaling in the effects of AT on airway inflammation, remodeling and hyperresponsiveness in a model of allergic airway inflammation.
METHODS:C57Bl/6 mice were divided into Control (Co), Exercise (Ex), HDM (HDM), and HDM+Exercise (HDM+ Ex). Dermatophagoides pteronyssinus (100ug/mouse) were administered oro-tracheally on days 0, 7, 14, 21, 28, 35, 42 and 49. AT was performed in a treadmill during 4 weeks in moderate intensity, from day 24 until day 52.
RESULTS:AT inhibited HDM-induced total cells (p<0.001), eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in BAL, and eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in peribronchial space. AT also reduced BAL levels of IL-4 (p<0.001), IL-5 (p<0.001), IL-13 (p<0.001), CXCL1 (p<0.01), IL-17 (p<0.01), IL-23 (p<0.05), IL-33 (p<0.05), while increased IL- 10 (p<0.05). Airway collagen fibers (p<0.01), elastic fibers p<0.01) and mucin (p<0.01) were also reduced by AT. AT also inhibited HDM-induced airway hyperresponsiveness (AHR) to methacholine 6,25mg/ml (p<0.01), 12,5mg/mL (p<0.01), 25mg/mL (p<0.01) and 50mg/mL (p<0.01). Mechanistically, AT reduced the expression of STAT6 (p<0.05), STAT3 (p<0.001), STAT5 (p<0.01) and JAK2 (p<0.001), similarly by peribronchial leukocytes and by airway epithelial cells. SOCS1 expression (p<0.001) was upregulated in leukocytes and in epithelial cells, SOCS2 (p<0.01) was upregulated in leukocytes and SOCS3 down-regulated in leukocytes (p<0.05) and in epithelial cells (p<0.001).
CONCLUSIONS:AT reduces asthma phenotype involving SOCSJAK- STAT signaling.
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