Probiotic Lactobacillus casei activates innate immunity via NF-κB and p38 MAP kinase signaling pathways
Probiotic Lactobacillus casei activates innate immunity via NF-κB and p38 MAP kinase signaling pathways
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DOI：
10.1016/j.micinf.2005.10.019
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发表时间：
2006-04-01
影响因子：
5.8
通讯作者：
Danbara, Hirofurni
中科院分区：
文献类型：
--
作者：
Kim, Yun-Gi;Ohta, Toshihisa;Danbara, Hirofurni
益生菌是通过改善肠道微生物菌群平衡并可能通过增强宿主防御系统而有益于宿主的微生物。我们研究了益生菌干酪乳杆菌ATCC 27139在体内上调先天免疫应答的机制。利用系统性单核细胞增生李斯特菌感染和MethA纤维肉瘤肿瘤发生的小鼠模型，与BALB/c和SCID小鼠联合，我们发现，肠道外给予李斯特菌，casei ATCC 27139具有抗L.单核细胞增多症感染和抗肿瘤活性对MethA纤维肉瘤通过激活先天免疫，而L。从MNNG处理的克隆中选出的J1噬菌体抗性菌株--干酪素ATCC 27139-J1 R菌株缺乏这些活性。观察到ATCC 27139和ATCC 27139-J1 R菌株在通过脾细胞诱导先天性细胞因子（如TNF-α、IL-12、IL-18和IFN-γ）和病原体相关分子模式受体（TLR 2和Nod 2）的能力方面存在显著差异。此外，尽管在ATCC 27139和ATCC 27139-J1 R处理组中，脾脏中NF-κ B p65的磷酸化同样增强，但p38 MAPK和MAPK APK-2的磷酸化仅由ATCC 27139显著诱导。此外，NF-κ B（柳氮磺胺吡啶）和p38 MAPK（SB 203580）的抑制剂显著降低了用L.提示NF-κ B和p38 MAPK信号通路在益生菌L. casei ATCC 27139增强先天免疫中起重要作用。casei。(c)2006年，Elsevier SAS。All rights reserved.
Probiotic bacteria are microorganisms that benefit the host through improvement of the balance of intestinal microflora and possibly by augmentation of host defense systems. We examined the mechanisms for the up-regulation of innate immune responses by a probiotic Lactobacillus casei ATCC27139, in vivo. Using mouse models of systemic Listeria monocytogenes infection and MethA fibrosarcoma tumorigenesis in combination with BALB/c and SCID mice, we found that parenteral administration of L. casei ATCC27139 confers a protective effect against L. monocytogenes infection and anti-tumor activity against MethA fibrosarcoma by activation of innate immunity, while L. casei ATCC27139-J1R strains, which are J1 phage-resistant strains that have been selected from MNNG-treated clones, lacked these activities. Substantial differences between ATCC27139 and ATCC27139-J1R strains were observed in the capacity to induce innate cytokines such as TNF-alpha, IL-12, IL-18, and IFN-gamma, and pathogen-associated molecular pattern receptors, TLR2 and Nod2, by spleen cells. In addition, although phosphorylation of NF-KB p65 in spleen was equally enhanced in the ATCC27139- and the ATCC27139-J1R-treated groups, phosphorylation of both p38 MAPK and MAPKAPK-2 was significantly induced only by ATCC27139. Furthermore, inhibitors of NF-KB (sulfasalazine) and p38 MAPK (SB203580) significantly reduced cytokine production by the spleen cells of the mice treated with L. casei ATCC27139, suggesting that both NF-KB and p38 MAPK signaling pathways play important roles in the augmentation of innate immunity by the probiotic L. casei. (c) 2006 Elsevier SAS. All rights reserved.