Toki Shinji, Kagaya Shinji, Shinohara Miwa, Wakiguchi Hiroshi, Matsumoto Takashi, Takahata Yoshihisa, Morimatsu Fumiki, Saito Hirohisa, Matsumoto Kenji
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Int Arch Allergy Immunol. 2009;148(1):45-58. doi: 10.1159/000151505. Epub 2008 Aug 21.
Recently, some strains of lactic acid bacteria (LAB) have been reported to prevent the development of atopic dermatitis and to improve allergic symptoms, especially in young children. However, the mechanisms involved in these effects are not fully understood. Intestinal microbiota play critical roles in the development of host immune development and are recognized and regulated by the host through intestinal epithelial cells (IECs). We thus hypothesized that LAB influence the host immune system through the activation of IECs. To begin testing this hypothesis, chemokine expression in IECs exposed to intestinal bacteria was investigated.
Caco-2 cell monolayers were stimulated with different concentrations of various live or heat-killed intestinal bacteria or bacterial components for up to 3 h. Changes in the gene expressions of various chemokines were measured using quantitative real-time PCR.
The expressions of CCL20, CXCL8, CXCL10 and CX3CL1 were strongly induced by nonpathogenic Escherichia coli in a dose-dependent manner and were partially induced by some commensal LAB. In contrast, Lactobacillus rhamnosus GG (LGG) and Lactobacillus casei did not induce these chemokine expressions. In addition, LGG significantly suppressed the expressions of CCL20 and CXCL10 induced by E. coli, peptidoglycan or flagellin when cultured simultaneously.
LGG and L. casei markedly suppressed E. coli-induced chemokine expression, presumably through the suppression of the Toll-like receptor-mediated signal transduction pathway, at least in part. The clinical importance of this suppressive effect and the mechanisms involved require further investigation; however, such effects can be used as a marker to identify clinically useful LAB.
最近，有报道称某些乳酸菌（LAB）菌株可预防特应性皮炎的发展并改善过敏症状，尤其是在幼儿中。然而，这些作用所涉及的机制尚未完全了解。肠道微生物群在宿主免疫发育中起关键作用，并通过肠上皮细胞（IECs）被宿主识别和调节。因此，我们假设乳酸菌通过激活IECs影响宿主免疫系统。为了开始验证这一假设，我们研究了暴露于肠道细菌的IECs中趋化因子的表达。
用不同浓度的各种活的或热灭活的肠道细菌或细菌成分刺激Caco-2细胞单层长达3小时。使用定量实时PCR测量各种趋化因子基因表达的变化。
非致病性大肠杆菌以剂量依赖的方式强烈诱导CCL20、CXCL8、CXCL10和CX3CL1的表达，一些共生LAB也部分诱导了这些表达。相比之下，鼠李糖乳杆菌GG（LGG）和干酪乳杆菌未诱导这些趋化因子的表达。此外，当同时培养时，LGG显著抑制了大肠杆菌、肽聚糖或鞭毛蛋白诱导的CCL20和CXCL10的表达。
LGG和干酪乳杆菌明显抑制大肠杆菌诱导的趋化因子表达，推测至少部分是通过抑制Toll样受体介导的信号转导途径。这种抑制作用的临床重要性及其涉及的机制需要进一步研究；然而，这种作用可作为鉴定临床上有用的LAB的标志物。
