Frick Julia-Stefanie, Schenk Katrin, Quitadamo Matteo, Kahl Frauke, Köberle Martin, Bohn Erwin, Aepfelbacher Martin, Autenrieth Ingo B
Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.
Inflamm Bowel Dis. 2007 Jan;13(1):83-90. doi: 10.1002/ibd.20009.
Lactobacilli represent a major component of the human microbiota. In this study we investigated whether and how Lactobacillus fermentum inhibits the proinflammatory responses of human epithelial cells on Yersinia enterocolitica infection.
Human epithelial cells were exposed to Y. enterocolitica pYV(-) or L. fermentum or to both strains, combinations of heat-killed L. fermentum or supernatant of L. fermentum cultures and Y. enterocolitica. The modulation of Y. enterocolitica induced IL-8 levels in the culture supernatants was determined and activation of Rac, p38, and NF-kappaB was investigated.
Exposure of human epithelial cells to L. fermentum does not induce NF-kappaB activation and subsequent IL-8 secretion in HeLa cells, whereas Y. enterocolitica induces NF-kappaB activation and high levels of IL-8. Viable L. fermentum, supernatant of L. fermentum cultures, but not heat-killed L. fermentum, inhibited IL-8 secretion of HeLa cells triggered by Y. enterocolitica. Lactobacillus fermentum-exposed HeLa cells showed decreased Rac, p38, and NF-kappaB activation after Y. enterocolitica infection. Treatment of L. fermentum supernatants with phospholipase C abolished the inhibitory effect, indicating that a secreted phospholipid mediates the antiinflammatory properties of L. fermentum. Adhesion to or invasion of Y. enterocolitica into epithelial cells was not altered by coincubation with L. fermentum.
Our results lead to the conclusion that L. fermentum inhibits the Y. enterocolitica-induced IL-8 production by a possibly secreted phospholipid of <10 kDa molecular weight. These data suggest that L. fermentum may have probiotic properties modulating intestinal inflammatory responses and might offer new therapeutic strategies in the treatment of intestinal inflammatory diseases.
乳酸杆菌是人类微生物群的主要组成部分。在本研究中，我们调查了发酵乳杆菌是否以及如何抑制人上皮细胞对小肠结肠炎耶尔森菌感染的促炎反应。
将人上皮细胞暴露于小肠结肠炎耶尔森菌pYV(-)或发酵乳杆菌或两种菌株，热灭活发酵乳杆菌或发酵乳杆菌培养上清液与小肠结肠炎耶尔森菌的组合。测定小肠结肠炎耶尔森菌诱导的培养上清液中IL-8水平的调节，并研究Rac、p38和NF-κB的激活情况。
人上皮细胞暴露于发酵乳杆菌不会在HeLa细胞中诱导NF-κB激活和随后的IL-8分泌，而小肠结肠炎耶尔森菌会诱导NF-κB激活和高水平的IL-8。活的发酵乳杆菌、发酵乳杆菌培养上清液，但不是热灭活的发酵乳杆菌，抑制了小肠结肠炎耶尔森菌触发的HeLa细胞的IL-8分泌。暴露于发酵乳杆菌的HeLa细胞在小肠结肠炎耶尔森菌感染后显示Rac、p38和NF-κB激活减少。用磷脂酶C处理发酵乳杆菌上清液消除了抑制作用，表明分泌的磷脂介导了发酵乳杆菌的抗炎特性。与发酵乳杆菌共孵育不会改变小肠结肠炎耶尔森菌对上皮细胞的粘附或侵袭。
我们的结果得出结论，发酵乳杆菌通过一种可能分泌的分子量<10 kDa的磷脂抑制小肠结肠炎耶尔森菌诱导的IL-8产生。这些数据表明，发酵乳杆菌可能具有调节肠道炎症反应的益生菌特性，并可能为治疗肠道炎症性疾病提供新的治疗策略。
