Chung Y W, Choi J H, Oh T-Y, Eun C S, Han D S
Department of Gastroenterology, Hallym University Sacred Heart Hospital, Anyang, Korea.
Clin Exp Immunol. 2008 Jan;151(1):182-9. doi: 10.1111/j.1365-2249.2007.03549.x. Epub 2007 Nov 15.
Probiotics, defined as live or attenuated bacteria or bacterial products, confer a significant health benefit to the host. Recently, they have been shown to be useful in the treatment of chronic inflammatory bowel disease and infectious colitis. In this study, we investigated the effect of probiotics on the development of experimental colitis using Toll-like receptor 4 (TLR-4) mutant (lps-/lps-) mice. TLR-4(lps-/lps-) and wild-type (WT) mice were given 2.5% dextran sulphate sodium (DSS) in drinking water to induce colitis with or without Lactobacillus casei pretreatment. Clinical and histological activity of DSS-colitis was attenuated markedly both in TLR-4(lps-/lps-) and WT mice pretreated with L. casei. Interestingly, histological activity was less severe in TLR-4(lps-/lps-) mice than in WT mice. The levels of myeloperoxidase activity and interleukin (IL)-12p40 were attenuated in pretreated TLR-4(lps-/lps-) mice after DSS administration. By contrast, transforming growth factor (TGF)-beta and IL-10 mRNA and protein expressions were increased markedly in pretreated TLR-4(lps-/lps-) mice. The current results suggest that L. casei has a preventive effect in the development of acute DSS-induced colitis and its action depends largely upon TLR-4 status. L. casei modulates the expression of inflammatory cytokines and down-regulates neutrophilic infiltration in the case of incomplete TLR-4 complex signalling.
益生菌被定义为活的或减毒的细菌或细菌产物,能给宿主带来显著的健康益处。最近,它们已被证明可用于治疗慢性炎症性肠病和感染性结肠炎。在本研究中,我们使用Toll样受体4(TLR - 4)突变(lps - /lps - )小鼠研究了益生菌对实验性结肠炎发展的影响。给TLR - 4(lps - /lps - )和野生型(WT)小鼠饮用含2.5%硫酸葡聚糖钠(DSS)的水以诱导结肠炎,同时进行或不进行干酪乳杆菌预处理。在接受干酪乳杆菌预处理的TLR - 4(lps - /lps - )和WT小鼠中,DSS诱导的结肠炎的临床和组织学活性均明显减弱。有趣的是,TLR - 4(lps - /lps - )小鼠的组织学活性比WT小鼠轻。给予DSS后,预处理的TLR - 4(lps - /lps - )小鼠的髓过氧化物酶活性和白细胞介素(IL)- 12p40水平降低。相比之下,预处理的TLR - 4(lps - /lps - )小鼠中转化生长因子(TGF)-β和IL - 10的mRNA及蛋白表达明显增加。目前的结果表明,干酪乳杆菌对急性DSS诱导的结肠炎的发展具有预防作用,其作用很大程度上取决于TLR - 4状态。在TLR - 4复合体信号不完全的情况下,干酪乳杆菌可调节炎性细胞因子的表达并下调嗜中性粒细胞浸润。