کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3296601 1209871 2007 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Prevention and Treatment of Colitis With Lactococcus lactis Secreting the Immunomodulatory Yersinia LcrV Protein
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Prevention and Treatment of Colitis With Lactococcus lactis Secreting the Immunomodulatory Yersinia LcrV Protein
چکیده انگلیسی

Background & Aims: The low calcium response V (LcrV) protein synthesized by gram-negative, pathogenic yersiniae participates in bacterial evasion of the host’s innate immune response by stimulating synthesis of the anti-inflammatory interleukin (IL)-10 and preventing the activation of proinflammatory cytokines. Methods: We genetically engineered the food-grade bacterium Lactococcus lactis to secrete the LcrV protein from the enteropathogenic species Yersinia pseudotuberculosis. The protective and therapeutic potential of orally administered LcrV-secreting L lactis was evaluated in 2 models of acute experimental colitis (induced by trinitrobenzene sulfonic acid [TNBS] and dextran sodium sulfate [DSS], respectively) in wild-type and knockout mice. Results: Oral administration of LcrV-secreting L lactis led to active delivery of LcrV and induction of IL-10 (via a Toll-like receptor 2–dependent pathway) in the colon and prevented TNBS-induced colitis, in contrast to the L lactis control not producing LcrV. Down-regulation of tissue inflammatory markers correlated well with the reduction in damage to the colonic mucosa. In contrast, TNBS-induced colitis was not prevented in IL-10−/− mice pretreated with LcrV-secreting L lactis, thus showing that IL-10 is required for LcrV protection. Administration of LcrV-secreting L lactis also proved to be very effective in preventing and treating acute DSS-induced colitis. Conclusions: LcrV-secreting L lactis decreased experimentally induced intestinal inflammation in 2 murine models of colitis. This novel approach highlights the potential of using pathogen-derived immunomodulating molecules in vivo as novel therapeutics for inflammatory bowel diseases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 133, Issue 3, September 2007, Pages 862–874
نویسندگان
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