Lim S-M, Jang H M, Jang S-E, Han M J, Kim D-H
1 Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, 26, Kyungheedaero, Dongdaemun-gu, Seoul 02447, Korea.
2 Department of Food and Nutrition, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
Benef Microbes. 2017 May 30;8(3):407-419. doi: 10.3920/BM2016.0156. Epub 2017 May 15.
In the present study, we isolated Lactobacillus fermentum IM12 from human gut microbiota, which strongly inhibited interleukin (IL)-6 expression and STAT3 activation in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages, and examined its anti-inflammatory effect in mice with carrageenan-induced hind-paw oedema (CIE) or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis (TIC). Oral administration of IM12 (0.2×10, 1×10 or 5×10 cfu/mouse, once a day for 3 days) in mice with CIE significantly suppressed the increase of oedema volume and thickness, as well as myeloperoxidase activity and IL-6, IL-17, NO, and prostaglandin E2 levels in the carrageenan-stimulated paw. Treatment with IM12 (1×10 cfu/mouse, once a day for 3 days) in mice with TIC significantly suppressed colon shortening, and myeloperoxidase activity and IL-6 and IL-17 levels. Treatment with IM12 in mice with CIE or TIC also suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, as well as activation of nuclear factor kappa beta (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Furthermore, IM12 significantly inhibited the expression of iNOS, and COX-2, as well as activation of NF-κB in LPS-stimulated mouse peritoneal macrophages. The inflammatory effect of heat-inactivated IM12 was significantly different to that of live IM12 in mice with TIC, although anti-inflammatory effect of IM12 was reduced by heat treatment. Based on these findings, IM12 may attenuate inflammation by inhibiting NF-κB-STAT3 signalling pathway.
在本研究中，我们从人体肠道微生物群中分离出发酵乳杆菌IM12，它能强烈抑制脂多糖（LPS）刺激的小鼠腹腔巨噬细胞中白细胞介素（IL）-6的表达和信号转导子和转录激活子3（STAT3）的激活，并研究了其对角叉菜胶诱导的后爪水肿（CIE）或2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎（TIC）小鼠的抗炎作用。在CIE小鼠中口服IM12（0.2×10、1×10或5×10 cfu/小鼠，每天一次，共3天）可显著抑制水肿体积和厚度的增加，以及角叉菜胶刺激的爪子中的髓过氧化物酶活性和IL-6、IL-17、一氧化氮（NO）和前列腺素E2水平。在TIC小鼠中用IM12（1×10 cfu/小鼠，每天一次，共3天）治疗可显著抑制结肠缩短以及髓过氧化物酶活性和IL-6及IL-17水平。在CIE或TIC小鼠中用IM12治疗还可抑制诱导型NO合酶（iNOS）和环氧化酶（COX）-2的表达，以及核因子κB（NF-κB）和STAT3的激活。此外，IM12可显著抑制LPS刺激的小鼠腹腔巨噬细胞中iNOS和COX-2的表达以及NF-κB的激活。在TIC小鼠中，热灭活的IM12的炎症作用与活IM12的炎症作用显著不同，尽管热处理会降低IM12的抗炎作用。基于这些发现，IM12可能通过抑制NF-κB-STAT3信号通路来减轻炎症。
