Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Pediatrics, Chi-Mei Medical Center, Liou-Yin, Tainan, Taiwan.
J Mol Med (Berl). 2018 Jan;96(1):39-51. doi: 10.1007/s00109-017-1598-1. Epub 2017 Oct 14.
Lactobacilli prevent the early development of allergic diseases in children and experimental asthma in mice. However, the detailed mechanism underlying this action remains unknown. We aimed to explore the activation pathway in the host by Lactobacillus and identify its immunomodulation mechanism in allergic asthma. Continuous administration of 10 cfu, but not 10 cfu, of L. gasseri for 4 weeks prevented Dermatophagoides pteronyssinus (Der p)-induced airway hypersensitivity and inflammation in a mouse model of allergic asthma. DNA microarray analysis of the mesenteric and lung draining lymph nodes revealed a significant decrease in inflammatory chemokines and increase in gene expression in carbohydrate and lipid metabolism, particularly of PPARγ, in 10 cfu L. gasseri-administered mice compared with untreated mice. Compared with WT mice, Der p-sensitized PPARγ mice showed increased airway hyperresponsiveness to methacholine, inflammatory cell infiltration, and inflammatory cytokine secretion in bronchoalveolar fluid. Moreover, the protective effects of L. gasseri were lost in Der p-induced airway inflammation in PPARγ mice, and L. gasseri-induced PPARγ activation in BMDCs inhibited the development of allergic airway inflammation in both PPARγ WT and PPARγ mice. L. gasseri may act via a novel PPARγ activation pathway in DCs to alleviate allergen-induced airway inflammation in allergic asthma.
L. gasseri prevents mite allergen (Der p)-induced airway inflammation. Prevention of airway inflammation occurs via activation of PPARγ in dendritic cells. L. gasseri administration does not reverse Der p-induced airway inflammation in PPARγ mice. L. gasseri-induced PPARγ activation inhibits development of airway inflammation in WT and PPARγ mice.
乳杆菌可预防儿童过敏疾病和实验性哮喘的早期发展。然而，其作用的详细机制尚不清楚。我们旨在探索乳杆菌在宿主中的激活途径，并确定其在过敏性哮喘中的免疫调节机制。连续给予 10 cfu 而不是 10 cfu 的格氏乳杆菌 4 周可预防变应原性哮喘小鼠模型中尘螨（Der p）诱导的气道高反应性和炎症。肠系膜和肺引流淋巴结的 DNA 微阵列分析显示，与未处理的小鼠相比，10 cfu 格氏乳杆菌给药小鼠的炎症趋化因子显著减少，碳水化合物和脂质代谢中的基因表达增加，特别是 PPARγ。与 WT 小鼠相比，Der p 致敏的 PPARγ 小鼠对乙酰甲胆碱的气道高反应性增加，支气管肺泡灌洗液中的炎症细胞浸润和炎症细胞因子分泌增加。此外，在 PPARγ 小鼠的 Der p 诱导的气道炎症中，L. gasseri 的保护作用丧失，并且 L. gasseri 在 BMDCs 中诱导的 PPARγ 激活抑制了 PPARγ WT 和 PPARγ 小鼠的过敏性气道炎症的发展。L. gasseri 可能通过 DC 中的新型 PPARγ 激活途径发挥作用，以减轻过敏性哮喘中过敏原诱导的气道炎症。
L. gasseri 可预防螨过敏原（Der p）诱导的气道炎症。气道炎症的预防是通过树突状细胞中 PPARγ 的激活来实现的。L. gasseri 给药不能逆转 PPARγ 小鼠 Der p 诱导的气道炎症。L. gasseri 诱导的 PPARγ 激活抑制 WT 和 PPARγ 小鼠气道炎症的发展。
