One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.
- MeSH
- akutní nemoc MeSH
- antigeny CD11b biosyntéza genetika MeSH
- aplikace rektální MeSH
- bakteriální translokace MeSH
- butyráty metabolismus MeSH
- Clostridium tyrobutyricum fyziologie MeSH
- fosfoproteiny biosyntéza genetika MeSH
- imunokompetence MeSH
- interleukin-18 biosyntéza genetika MeSH
- kolon metabolismus mikrobiologie patologie MeSH
- mastné kyseliny metabolismus MeSH
- membránové proteiny biosyntéza genetika MeSH
- mucin 2 biosyntéza genetika MeSH
- muciny biosyntéza MeSH
- myši inbrední BALB C MeSH
- myši SCID MeSH
- myši MeSH
- organismy bez specifických patogenů MeSH
- probiotika terapeutické užití MeSH
- síran dextranu toxicita MeSH
- těžká kombinovaná imunodeficience genetika imunologie MeSH
- TNF-alfa biosyntéza genetika MeSH
- ulcerózní kolitida chemicky indukované genetika imunologie mikrobiologie patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This study was aimed to evaluate the role of commensal Gram-negative bacterium Bacteroides ovatus in murine model of chronic intestinal inflammation. The attempt to induce chronic colitis was done in Bacteroides ovatus-monoassociated, germ-free and conventional mice either in immunocompetent (BALB/c) mice or in mice with severe combined immunodeficiency (SCID), using 2.5 % dextran-sodium sulfate (DSS) in drinking water (7 days DSS, 7 days water, 7 days DSS). Conventional mice developed chronic colitis. Some of germ-free BALB/c and the majority of germ-free SCID mice did not survive the long-term treatment with DSS due to massive bleeding into the intestinal lumen. However, monocolonization of germ-free mice of both strains with Bacteroides ovatus prior to long-term treatment with DSS protected mice from bleeding, development of intestinal inflammation and precocious death. We observed that though DSS-treated Bacteroides ovatus-colonized SCID mice showed minor morphological changes in colon tissue, jejunal brush-border enzyme activities such as gamma-glutamyltranspeptidase, lactase and alkaline phosphatase were significantly reduced in comparison with DSS-untreated Bacteroides ovatus-colonized mice. This modulation of the enterocyte gamma-glutamyltranspeptidase localized to the brush border membrane has been described for the first time. This enzyme is known to reflect an imbalance between pro-oxidant and anti-oxidant mechanisms, which could be involved in protective effects of colonization of germ-free mice with Bacteroides ovatus against DSS injury.
- MeSH
- alkalická fosfatasa metabolismus MeSH
- Bacteroides růst a vývoj MeSH
- časové faktory MeSH
- chronická nemoc MeSH
- financování organizované MeSH
- gama-glutamyltransferasa MeSH
- jejunum enzymologie MeSH
- kolitida MeSH
- kolon mikrobiologie patologie MeSH
- laktasa metabolismus MeSH
- mikroklky enzymologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši SCID MeSH
- myši MeSH
- síran dextranu MeSH
- střevní sliznice enzymologie MeSH
- stupeň závažnosti nemoci MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
Germ-free immunocompetent (BALB/c) and immunodeficient (SCID) mice were colonized either by E. coli O6K13 or by E. coli strain Nissle 1917 and intestinal inflammation was induced by administering 2.5% dextran sulfate sodium (DSS) in drinking water. Controls were germ-free mice which demonstrated only mild inflammatory changes after induction of an acute intestinal inflammation with DSS as compared with conventional mice in which acute colitis of the colon mucosa similar to human ulcerative colitis is elicited. In mice monocolonized with the nonpathogenic E. coli Nissle 1917 the inflammatory disease did not develop (damage grade 0) while animals monocolonized with uropathogenic E. coli O6K13 exhibited inflammatory changes similar to those elicited in conventionally reared mice (damage grade 3). In the chronic inflammation model, immunocompetent BALB/c mice monocolonized with E. coli Nissle 1917 showed no conspicuous inflammatory changes of the colon mucosa whereas those monocolonized with E. coli O6K13 developed colon inflammation associated with marked infiltration of inflammatory cells. In contrast to germ-free immunodeficient SCID mice that died after application of DSS, the colon mucosa of SCID mice monoassociated with E. coli Nissle 1917 exhibited only moderate inflammatory changes which were less pronounced than changes of colon mucosa of SCID mice monoassociated with E. coli O6K13.
- MeSH
- Escherichia coli růst a vývoj účinky léků MeSH
- financování organizované využití MeSH
- idiopatické střevní záněty komplikace mikrobiologie patofyziologie MeSH
- imunohistochemie metody využití MeSH
- interferony MeSH
- interleukin-2 MeSH
- kolitida komplikace mikrobiologie patologie MeSH
- mikrobiologické techniky metody využití MeSH
- myši inbrední BALB C mikrobiologie růst a vývoj MeSH
- myši SCID mikrobiologie růst a vývoj MeSH
- síran dextranu farmakologie škodlivé účinky MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- gnotobiologické modely MeSH
- histologie MeSH
- kolon mikrobiologie patologie MeSH
- myši MeSH
- syndromy imunologické nedostatečnosti komplikace MeSH
- ulcerózní kolitida chemicky indukované imunologie patologie MeSH
- zánět etiologie patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
157 listů : ilustrace, tabulky ; 30 cm + 5 nečíslovaných vložených karet obrazové přílohy
Dizertační práce, která se zaměřuje na imunologické aspekty a patogenezi idiopatických střevních zánětů a ulcerózní kolitidy na myších modelech.
- MeSH
- idiopatické střevní záněty etiologie MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- slizniční imunita MeSH
- ulcerózní kolitida etiologie MeSH
- Check Tag
- myši MeSH
- Publikační typ
- vysokoškolské kvalifikační práce MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- alergologie a imunologie
- experimentální medicína
- MeSH
- dextrany MeSH
- Escherichia coli MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- ulcerózní kolitida etiologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- kongresy MeSH
- srovnávací studie MeSH
