Lipoxin A4 (LXA4) is considered a specialised pro-resolving mediator that decreases inflammation: however, pro-inflammatory effects have been described in the airways. Here, we investigated whether LXA4 could influence airway hyperreactivity induced in mouse trachea by house dust mite extract (HDM) or TNFα. Intranasal instillation of HDM caused a serotonin (5-HT) mediated airway hyperreactivity ex vivo (Emax: 78.1 ± 16.2 % versus control 12.8 ± 1.0 %) that was reduced by LXA4 installation one hour prior to HDM (Emax: 49.9 ± 11.4 %). Also, in isolated tracheal segments cultured for four days, HDM induced a hyperreactivity (Emax: 33.2 ± 3.1 % versus control 9.0 ± 0.7 %) that was decreased by LXA4 (Emax: 18.7 ± 1.5 %). One part of the HDM-induced hyperreactivity could be inhibited by the TNFα-inhibitor etanercept. TNFα-induced upregulation of 5-HT responses (Emax: 51.3 ± 1.2 % versus control 13.9 ± 0.5 %) was decreased by 10-1000 nM LXA4. In precontracted tracheal segments, LXA4 had no relaxing effect. Overall, LXA4 was able to decrease airway hyperreactivity induced by both HDM and TNFα, thus having a sub-acute anti-inflammatory effect in airway inflammation.

中文翻译：

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Lipoxin A4可减少小鼠气管中的屋尘螨和TNFα诱导的反应过度。

Lipoxin A4（LXA4）被认为是减少炎症的专门的促炎症介质：但是，已在气道中描述了促炎作用。在这里，我们调查了LXA4是否可以影响由室内尘螨提取物（HDM）或TNFα诱导的小鼠气管气道高反应性。鼻内滴入HDM导致5-羟色胺（5-HT）介导的离体气道高反应性（Emax：78.1±16.2％vs对照12.8±1.0％），在HDM之前一小时安装LXA4可降低（Emax：49.9±11.4％） 。同样，在培养四天的孤立气管节段中，HDM引起的高反应性（Emax：33.2±3.1％，而对照为9.0±0.7％）被LXA4降低（Emax：18.7±1.5％）。TNFα抑制剂依那西普可抑制一部分HDM诱导的高反应性。10-1000 nM LXA4降低了TNFα诱导的5-HT应答上调（Emax：51.3±1.2％，相对于对照13.9±0.5％）。在预收缩的气管段中，LXA4没有松弛作用。总体而言，LXA4能够降低HDM和TNFα诱导的气道高反应性，因此在气道炎症中具有亚急性抗炎作用。