Probiotic lactobacilli and VSL#3 induce enterocyte β-defensin 2
Probiotic lactobacilli and VSL#3 induce enterocyte β-defensin 2
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DOI：
10.1111/j.1365-2249.2007.03587.x
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发表时间：
2008-03-01
影响因子：
4.6
通讯作者：
Fellermann, K.
中科院分区：
文献类型：
--
作者：
Schlee, M.;Harder, J.;Fellermann, K.
最近的证据表明，益生菌可以通过诱导抗微生物肽如防御素来稳定肠道屏障功能。本研究旨在阐明不同益生菌菌株对人β防御素-2（hBD-2）基因的诱导机制。hBD-2 mRNA的表达在Caco-2细胞处理后孵育6 h达到峰值，并随着各种益生菌剂量的增加而增加。hBD-2启动子上的核因子（NF）-κ B和激活蛋白-1（AP-1）结合位点的缺失导致益生菌对启动子激活的完全废除。如通过使用特异性丝裂原活化蛋白激酶（MAPK）抑制剂所揭示的，hBD-2诱导依赖于MAPK细胞外调节激酶（ERK 1/2）、p38和c-Jun N-末端激酶（JNK），尽管程度不同。如酶联免疫吸附测定（ELISA）所示，几种乳杆菌属菌株和VSL#3（四种乳杆菌、三种双歧杆菌和一种链球菌属物种的益生菌混合物）诱导hBD-2肽分泌到培养基中。因此，本研究表明，乳酸杆菌和VSL#3细菌混合物通过诱导促炎途径（包括NF-κ B和AP-1以及MAPK）上调hBD-2来增强肠屏障功能。
Recent evidence suggests that probiotic bacteria may stabilize gut barrier function via induction of anti-microbial peptides such as defensins. This study aimed to elucidate the induction mechanism of the human beta defensin-2 (hBD-2) gene by different probiotic lactobacillus strains. The expression of hBD-2 mRNA peaked at 6 h of incubation upon treatment of Caco-2 cells and increased with higher dosage of various probiotic bacteria. Deletion of nuclear factor (NF)-kappa B and activator protein-1 (AP-1) binding sites on the hBD-2 promoter resulted in a complete abrogation of promoter activation by probiotics. As revealed by the use of specific mitogen-activated protein kinase (MAPK) inhibitors the hBD-2 induction was dependent on the MAPK extracellular regulated kinase (ERK 1/2), p38 and c-Jun N-terminal kinase (JNK), although to varying degrees. Several Lactobacillus strains and VSL#3, a probiotic cocktail of four lactobacilli, three bifidum and one streptococcus species, induced the secretion of the hBD-2 peptide into the culture media as shown by enzyme-linked immunosorbent assay (ELISA). Thus, the present study suggests that lactobacilli and the VSL#3 bacterial mixture strengthen intestinal barrier functions through the up-regulation of hBD-2 via induction of proinflammatory pathways including NF-kappa B and AP-1 as well as MAPKs.