Moonlighting glyceraldehyde-3-phosphate dehydrogenase of Lactobacillus gasseri inhibits keratinocyte apoptosis and skin inflammation in experimental atopic dermatitis.

IF 2.3 4区 医学 Q3 ALLERGY Asian Pacific journal of allergy and immunology Pub Date : 2024-05-06 DOI:10.12932/AP-211123-1733
Pei-Chi Chen, Miao-Hsi Hsieh, Wei-Leng Chen, Yu-Pu Hsia, Wen-Shou Kuo, Lawrence Shih-Hsin Wu, Shulhn-Der Wang, Xiao-Yu Liu, Jiu-Yao Wang, Hui-Fang Kao
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Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood.

Objective: Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management.

Methods: In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines.

Results: L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway.

Conclusion: The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

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加塞乳杆菌的月光甘油醛-3-磷酸脱氢酶可抑制实验性特应性皮炎的角质细胞凋亡和皮肤炎症。
背景:乳酸菌可作为益生菌预防或治疗各种疾病,而德尔布鲁贝克乳杆菌对特应性疾病的发生有抑制作用:本研究探讨了服用 L. delbrueckii 亚种乳杆菌菌株 LDL557 对由 Dermatophoides pteronyssinus(Der p)致敏引起的小鼠哮喘模型的影响,并调查了相关的肠道微生物群:方法:在BALB/c小鼠对Der p过敏后,每天口服三种不同剂量的LDL557(低剂量,107个菌落形成单位(CFU);中剂量,108个菌落形成单位;高剂量,109个菌落形成单位)和热处理杀死的LDL557(109个细胞)于200μL的PBS中,从Der p过敏前2周开始,持续4周。过敏原挑战后,评估气道对甲氧胆碱的反应性和炎症细胞流入肺部的情况。通过对小鼠粪便样本的 16S rRNA 基因 V3-V4 区域进行测序,获得了肠道微生物组:结果:活体(109 CFU)和热杀灭(109 个细胞)条件下的 LDL557 可降低小鼠在甲基胆碱刺激下的气道高反应性、炎症细胞浸润和粘液分泌。这些效果与地塞米松治疗组相似。LDL557治疗后,肠道微生物群没有发生明显变化,只是热处理后的LDL557比活体LDL557更容易改变肠道微生物谱:总之,我们发现活体和热处理后的 LDL557 在哮喘小鼠模型中具有预防 Der p 诱导的过敏性炎症的有益作用。
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来源期刊
CiteScore
12.80
自引率
0.00%
发文量
74
审稿时长
>12 weeks
期刊介绍: The Asian Pacific Journal of Allergy and Immunology (APJAI) is an online open access journal with the recent impact factor (2018) 1.747 APJAI published 4 times per annum (March, June, September, December). Four issues constitute one volume. APJAI publishes original research articles of basic science, clinical science and reviews on various aspects of allergy and immunology. This journal is an official journal of and published by the Allergy, Asthma and Immunology Association, Thailand. The scopes include mechanism, pathogenesis, host-pathogen interaction, host-environment interaction, allergic diseases, immune-mediated diseases, epidemiology, diagnosis, treatment and prevention, immunotherapy, and vaccine. All papers are published in English and are refereed to international standards.
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