Intra-Airway Treatment with Synthetic Lipoxin A4 and Resolvin E2 Mitigates Neonatal Asthma Triggered by Maternal Exposure to Environmental Particles.
Intra-Airway Treatment with Synthetic Lipoxin A4 and Resolvin E2 Mitigates Neonatal Asthma Triggered by Maternal Exposure to Environmental Particles.
复制标题
DOI：
10.3390/ijms24076145
复制
发表时间：
2023-03-24
影响因子：
5.6
通讯作者：
Fedulov, Alexey V.
中科院分区：
文献类型：
--
作者：
Ramar, Mohankumar;Yano, Naohiro;Fedulov, Alexey V.
关键词：
空气中的颗粒物会加剧哮喘患者的呼吸道炎症(AI)；此外，产前暴露于浓缩的城市空气颗粒物(CAPS)和柴油废气颗粒物(DEPS)会使后代容易患哮喘，并降低AI对过敏原的反应能力。我们之前测试了这样的假设，即这种暴露损害了对解决问题至关重要的专门的促分解介质的途径，并发现在暴露于风险的母亲的幼崽中，脂氧素A4(LxA4)和解析素E2(RvE2)水平下降。在这里，我们假设通过呼吸道补充合成的LxA4或RvE2可以改善过敏原暴露后的AI，这还没有在有环境毒物触发的模型中进行测试。出生前暴露于CAPS和DEPS导致哮喘易感性的BALB/c新生儿通过鼻内滴注750 ng/只LxA4或300 ng/只RvE2，每天治疗一次，为期3天，并使用故意低剂量的卵清蛋白方案进行测试，该方案会在暴露于颗粒物的母亲的后代中诱发哮喘，但不会引起对照母亲的哮喘，这模拟了人类哮喘的神秘母体传播。LxA4和RvE2改善了哮喘的表型并提高了AI分辨率，这被认为是降低了气道嗜酸性粒细胞增多、肺组织浸润和促过敏细胞因子水平。
Particulate matter in the air exacerbates airway inflammation (AI) in asthma; moreover, prenatal exposure to concentrated urban air particles (CAPs) and diesel exhaust particles (DEPs) predisposes the offspring to asthma and worsens the resolution of AI in response to allergens. We previously tested the hypothesis that such exposure impairs the pathways of specialized proresolving mediators that are critical for resolution and found declined Lipoxin A4 (LxA4) and Resolvin E2 (RvE2) levels in the “at-risk” pups of exposed mothers. Here, we hypothesized that supplementation with synthetic LxA4 or RvE2 via the airway can ameliorate AI after allergen exposure, which has not been tested in models with environmental toxicant triggers. BALB/c newborns with an asthma predisposition resultant from prenatal exposure to CAPs and DEPs were treated once daily for 3 days with 750 ng/mouse of LxA4 or 300 ng/mouse of RvE2 through intranasal instillation, and they were tested with the intentionally low-dose ovalbumin protocol that elicits asthma in the offspring of particle-exposed mothers but not control mothers, mimicking the enigmatic maternal transmission of asthma seen in humans. LxA4 and RvE2 ameliorated the asthma phenotype and improved AI resolution, which was seen as declining airway eosinophilia, lung tissue infiltration, and proallergic cytokine levels.
登录
查看更多内容
影响因子：
4.5
作者：
通讯作者：
--
DOI：
10.1165/rcmb.2009-0400oc
发表时间：
2011-03-01
影响因子：
6.4
作者：
Fedulov, Alexey V.;Kobzik, Lester
通讯作者：
Kobzik, Lester
影响因子：
24.3
作者：
Blacquiere, M. J.;Timens, W.;Hylkema, M. N.
通讯作者：
Hylkema, M. N.
专门的促解决介质：感染和炎症的内源性调节剂。
DOI：
10.1038/nri.2015.4
发表时间：
2016-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Basil MC;Levy BD
通讯作者：
Levy BD
DOI：
10.1111/j.1600-0897.2007.00496.x
发表时间：
2007-08-01
影响因子：
3.6
作者：
Fedulov, Alexey V.;Leme, Adriana S.;Kobzik, Lester
通讯作者：
Kobzik, Lester