肥胖增强变应性哮喘小鼠模型中非 Th2 气道炎症。

Obesity Enhances Non-Th2 Airway Inflammation in a Murine Model of Allergic Asthma.

机构信息

Department of Respiratory Sciences, Clinical Sciences, Glenfield Hospital, University of Leicester, Leicester LE3 9QP, UK.

出版信息

Int J Mol Sci. 2024 Jun 4;25(11):6170. doi: 10.3390/ijms25116170.

Abstract

Obese patients with asthma present with aggravated symptoms that are also harder to treat. Here, we used a mouse model of allergic asthma sensitised and challenged to house dust mite (HDM) extracts to determine whether high-fat-diet consumption would exacerbate the key features of allergic airway inflammation. C57BL/6 mice were intranasally sensitised and challenged with HDM extracts over a duration of 3 weeks. The impact of high-fat-diet (HFD) vs. normal diet (ND) chow was studied on HDM-induced lung inflammation and inflammatory cell infiltration as well as cytokine production. HFD-fed mice had greater inflammatory cell infiltration around airways and blood vessels, and an overall more severe degree of inflammation than in the ND-fed mice (semiquantitative blinded evaluation). Quantitative assessment of HDM-associated Th2 responses (numbers of lung CD4 T cells, eosinophils, serum levels of allergen-specific IgE as well as the expression of Th2 cytokines ( and )) did not show significant changes between the HFD and ND groups. Interestingly, the HFD group exhibited a more pronounced neutrophilic infiltration within their lung tissues and an increase in non-Th2 cytokines (, , , ). These findings provide additional evidence that obesity triggered by a high-fat-diet regimen may exacerbate asthma by involving non-Th2 and neutrophilic pathways.

摘要

肥胖的哮喘患者症状加重,且更难治疗。在这里,我们使用屋尘螨(HDM)提取物致敏和激发的过敏性哮喘小鼠模型来确定高脂肪饮食是否会加重过敏性气道炎症的关键特征。C57BL/6 小鼠经鼻腔致敏并接受 HDM 提取物激发,持续 3 周。研究了高脂肪饮食(HFD)与正常饮食(ND)对 HDM 诱导的肺炎症和炎症细胞浸润以及细胞因子产生的影响。与 ND 喂养组相比,HFD 喂养组气道和血管周围的炎症细胞浸润更多,炎症程度更严重(半定量盲法评估)。定量评估与 HDM 相关的 Th2 反应(肺 CD4 T 细胞、嗜酸性粒细胞数量、过敏原特异性 IgE 血清水平以及 Th2 细胞因子的表达)在 HFD 和 ND 组之间没有明显变化。有趣的是,HFD 组的肺组织中中性粒细胞浸润更明显,非 Th2 细胞因子(、、、)增加。这些发现提供了更多证据表明,高脂肪饮食引起的肥胖可能通过非 Th2 和中性粒细胞途径加重哮喘。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4e5/11172812/3d62068f8461/ijms-25-06170-g001.jpg

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