Lipopolysaccharide exposure makes allergic airway inflammation and hyper-responsiveness less responsive to dexamethasone and inhibition of iNOS
Lipopolysaccharide exposure makes allergic airway inflammation and hyper-responsiveness less responsive to dexamethasone and inhibition of iNOS
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DOI：
10.1111/j.1365-2222.2006.02514.x
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发表时间：
2006-07-01
影响因子：
6.1
通讯作者：
Losonczy, G.
中科院分区：
文献类型：
--
作者：
Komlosi, Z. I.;Pozsonyi, E.;Losonczy, G.
过敏性气道疾病可能对抗炎治疗无效，其原因尚不清楚。因此，在本实验中，我们检验了脂多糖（Lps）和过敏原共同暴露会导致糖皮质激素耐药性嗜酸性粒细胞气道炎症和高反应性（AHR）的假设。卵清蛋白 (Ova) 致敏的 BALB/c 小鼠在 Ova 攻击开始前 24 小时（连续 3 天 20 分钟）用 10 μg 鼻内 Lps 进行免疫。 Ova 挑战的最后 2 天给予地塞米松（5 毫克/公斤/天）。检查了 AHR、细胞积聚、支气管肺泡灌洗液 (BALF) 的细胞因子和亚硝酸盐浓度以及肺组织学。为了评估 iNOS 衍生的 NO 在气道反应性中的作用，在 AHR 测量前 2 小时用该酶的选择性抑制剂 (1400W) 处理小鼠。与未引发的过敏小鼠相比，经 Lps 引发的过敏小鼠发现更严重的嗜酸性粒细胞炎症和更高的亚硝酸盐形成。 Lps 启动后，BALF 中的 AHR 和 T 辅助细胞 2 型细胞因子浓度有所降低，但仍显着高于对照组。在 Lps 引发的过敏动物中，嗜酸性粒细胞炎症是部分的，而亚硝酸盐的产生和 AHR 在很大程度上对地塞米松具有耐药性。 1400W 有效且快速地降低了 Ova 致敏和攻击小鼠的 AHR，但在 Lps 启动加过敏后未能对其产生影响。总之，吸入 Lps 可能会加剧嗜酸性粒细胞炎症并降低过敏性气道疾病抗炎治疗的反应性。
Allergic airway disease can be refractory to anti-inflammatory treatment, whose cause is unclarified. Therefore, in the present experiment, we have tested the hypothesis that co-exposure to lipopolysacharide (Lps) and allergen results in glucocorticoid-resistant eosinophil airway inflammation and hyper-responsiveness (AHR). Ovalbumin (Ova)-sensitized BALB/c mice were primed with 10 mu g intranasal Lps 24 h before the start of Ova challenges (20 min on 3 consecutive days). Dexamethasone (5 mg/kg/day) was given on the last 2 days of Ova challenges. AHR, cellular build-up, cytokine and nitrite concentrations of bronchoalveolar lavage fluid (BALF) and lung histology were examined. To assess the role of iNOS-derived NO in airway responsiveness, mice were treated with a selective inhibitor of this enzyme (1400W) 2 h before AHR measurements. More severe eosinophil inflammation and higher nitrite formation were found in Lps-primed than in non-primed allergized mice. After Lps priming, AHR and concentrations of T-helper type 2 cytokines in BALF were decreased, but still remained significantly higher than in controls. Eosinophil inflammation was partially, while nitrite production and AHR were observed to be largely dexamethasone resistant in Lps-primed allergized animals. 1400W effectively and rapidly diminished the AHR in Ova-sensitized and challenged mice, but failed to affect it after Lps priming plus allergization. In conclusion, Lps inhalation may exaggerate eosinophil inflammation and reduce responsiveness to anti-inflammatory treatment in allergic airway disease.