Microbial Anti-Inflammatory Molecule (MAM) from Faecalibacterium prausnitzii Shows a Protective Effect on DNBS and DSS-Induced Colitis Model in Mice through Inhibition of NF-κB Pathway.
Microbial Anti-Inflammatory Molecule (MAM) from Faecalibacterium prausnitzii Shows a Protective Effect on DNBS and DSS-Induced Colitis Model in Mice through Inhibition of NF-κB Pathway.
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DOI：
10.3389/fmicb.2017.00114
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发表时间：
2017
影响因子：
5.2
通讯作者：
Chatel JM
中科院分区：
文献类型：
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作者：
Breyner NM;Michon C;de Sousa CS;Vilas Boas PB;Chain F;Azevedo VA;Langella P;Chatel JM
prausnitzii粪杆菌及其上清液对不同化学诱导结肠炎模型小鼠均有保护作用。最近，我们描述了在F. prausnitzii上清中发现的7个肽，它们都属于一种名为微生物抗炎分子（MAM）的蛋白质。这些肽在体外能抑制NF-κB通路，在体内对硫酸二硝基苯（DNBS）诱导的结肠炎模型具有抗炎作用。在本实验中，我们通过在NF-κB启动子控制下产生荧光素酶的转基因小鼠模型，在体内测试了MAM对NF-κB通路的影响。此外，我们在右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎中检测了该蛋白。为了研究MAM的作用，我们在真核启动子的控制下，给小鼠口服了一株携带含有MAM cDNA的质粒的乳酸乳球菌。乳杆菌将质粒传递到肠膜上皮细胞中，从而使宿主直接产生MAM。我们发现MAM在体内抑制NF-κB通路。我们证实了MAM在dnbs诱导的结肠炎和DSS模型中的抗炎作用。在DSS模型中，MAM能够抑制Th1和Th17的免疫应答，而在DNBS模型中，MAM能够降低Th1、Th2和Th17的免疫应答，并增加tgf - β的产生。
Faecalibacterium prausnitzii and its supernatant showed protective effects in different chemically-induced colitis models in mice. Recently, we described 7 peptides found in the F. prausnitzii supernatant, all belonging to a protein called Microbial Anti-inflammatory Molecule (MAM). These peptides were able to inhibit NF-κB pathway in vitro and showed anti-inflammatory properties in vivo in a DiNitroBenzene Sulfate (DNBS)-induced colitis model. In this current proof we tested MAM effect on NF-κB pathway in vivo, using a transgenic model of mice producing luciferase under the control of NF-κB promoter. Moreover, we tested this protein on Dextran Sodium Sulfate (DSS)-induced colitis in mice. To study the effect of MAM we orally administered to the mice a Lactococcus lactis strain carrying a plasmid containing the cDNA of MAM under the control of a eukaryotic promoter. L. lactis delivered plasmids in epithelial cells of the intestinal membrane allowing thus the production of MAM directly by host. We showed that MAM administration inhibits NF-κB pathway in vivo. We confirmed the anti-inflammatory properties of MAM in DNBS-induced colitis but also in DSS model. In DSS model MAM was able to inhibit Th1 and Th17 immune response while in DNBS model MAM reduced Th1, Th2, and Th17 immune response and increased TGFβ production.