BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.

• Klíčová slova
• I-FABP, claudin-3, clinically isolated syndrome, intestinal permeability, multiple sclerosis,
• MeSH
• biologické markery krev   MeSH
• claudin-3 * krev   MeSH
• dospělí MeSH
• funkce střevní bariéry MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• permeabilita MeSH
• proteiny vázající mastné kyseliny * krev   MeSH
• roztroušená skleróza * patofyziologie   krev   farmakoterapie   MeSH
• střevní sliznice * metabolismus   patofyziologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• claudin-3 * MeSH
• CLDN3 protein, human MeSH Prohlížeč
• proteiny vázající mastné kyseliny * MeSH

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
• protein zonula occludens 1 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
• Názvy látek
• antigeny CD11b MeSH
• butyráty MeSH
• fosfoproteiny MeSH
• interleukin-18 MeSH
• mastné kyseliny MeSH
• membránové proteiny MeSH
• Muc2 protein, mouse MeSH Prohlížeč
• mucin 2 MeSH
• muciny MeSH
• protein zonula occludens 1 MeSH
• síran dextranu MeSH
• Tjp1 protein, mouse MeSH Prohlížeč
• TNF-alfa MeSH

Interleukin-6 (IL-6) plays an important role in regulation of intestinal inflammatory processes in inflammatory bowel disease (IBD). The levels of IL-6 in media from cultured biopsy samples were determined by ELISA in 14 Crohn's disease (CD) patients, 17 patients with ulcerative colitis (UC), and 24 healthy controls in terminal ileum, cecum, and rectum. Results were confirmed by measuring mRNA expression in selected patients. In CD patients, there were increased levels of IL-6 (expressed in picograms per milligram of biopsy tissue mass) in terminal ileum compared with controls (median, 617 vs. 90.4; p < 0.001). High IL-6 levels were found in the rectum of CD patients with active disease but normal endoscopic findings (791 vs. 131; p < 0.05). This result was confirmed by mRNA expression. There was a substantial increase of IL-6 levels in cultured cecal (median, 327 vs. 94.0; p < 0.001) and rectal mucosa (median, 282 vs.131; p < 0.05) but not in ileal mucosa of UC patients. In conclusion, IL-6 production was higher in IBD patients than in controls; it correlated with disease activity and varied among different intestinal segments. In clinically active CD patients without rectal involvement, high IL-6 levels in cultured rectal mucosa suggest immune stimulation even in the absence of macroscopic inflammation.

• MeSH
• Crohnova nemoc imunologie   metabolismus   patologie   MeSH
• dospělí MeSH
• ELISA MeSH
• interleukin-6 biosyntéza   imunologie   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA biosyntéza   MeSH
• polymerázová řetězová reakce MeSH
• střevní sliznice imunologie   metabolismus   patologie   MeSH
• ulcerózní kolitida imunologie   metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• IL6 protein, human MeSH Prohlížeč
• interleukin-6 MeSH
• messenger RNA MeSH

OBJECTIVE: It is an open question whether multifunctional galectin-3 can be a serum marker in inflammatory bowel disease. METHODS: Western blots and commercial ELISA detected and quantitated the lectin immunocytochemistry using double labeling localized it in tissue sections. RESULTS: Serum concentrations were significantly increased in specimen of patients with active and remission-stage ulcerative colitis and Crohn's disease, associated with emerging positivity of CD14(+) cells. CONCLUSION: Enhanced concentration of galectin-3 in serum reflects presence of disease and points to its involvement in the pathogenesis.

• MeSH
• biologické markery MeSH
• Crohnova nemoc krev   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• Escherichia coli metabolismus   MeSH
• fluorescein-5-isothiokyanát MeSH
• fluorescenční barviva MeSH
• galektin 3 krev   MeSH
• idiopatické střevní záněty krev   chemicky indukované   diagnóza   MeSH
• imunohistochemie MeSH
• kolitida chemicky indukované   MeSH
• kolon metabolismus   MeSH
• lektiny metabolismus   MeSH
• lidé MeSH
• lipopolysacharidové receptory analýza   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• síran dextranu MeSH
• ulcerózní kolitida krev   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• fluorescein-5-isothiokyanát MeSH
• fluorescenční barviva MeSH
• galektin 3 MeSH
• lektiny MeSH
• lipopolysacharidové receptory MeSH
• síran dextranu MeSH

Dysregulation of innate and adaptive intestinal immune responses to bacterial microbiota is supposed to be involved in pathogenetic mechanisms of inflammatory bowel diseases (IBDs). We investigated expression of Toll-like receptor 2 (TLR2), TLR4, and their transmembrane coreceptor CD14 in biopsy samples from patients with IBD and in non-inflamed gut mucosa from controls. Small intestine and colon samples were obtained by colonoscopy from patients with Crohn's disease (CD), ulcerative colitis (UC), and controls. Immunohistochemical analysis of cryostat sections using polyclonal and monoclonal antibodies specific for TLR2, TLR4, and CD14 showed a significant increase in TLR2 expression in the terminal ileum of patients with inactive and active UC against controls. Significant upregulation of TLR4 expression relative to controls was found in the terminal ileum and rectum of UC patients in remission and in the terminal ileum of CD patients with active disease. CD14 expression was upregulated in the terminal ileum of CD patients in remission and with active disease, in the cecum of UC patients in remission and with active disease, and in rectum of UC patients with active disease. Hence, dysregulation of TLR2, TLR4, and CD14 expression in different parts of the intestinal mucosa may be crucial in IBD pathogenesis.

• MeSH
• biopsie MeSH
• cékum metabolismus   patologie   MeSH
• Crohnova nemoc metabolismus   patologie   MeSH
• ileum metabolismus   patologie   MeSH
• imunohistochemie MeSH
• lidé MeSH
• lipopolysacharidové receptory biosyntéza   MeSH
• rektum metabolismus   patologie   MeSH
• střevní sliznice metabolismus   patologie   MeSH
• toll-like receptor 2 biosyntéza   MeSH
• toll-like receptor 4 biosyntéza   MeSH
• ulcerózní kolitida metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lipopolysacharidové receptory MeSH
• TLR2 protein, human MeSH Prohlížeč
• TLR4 protein, human MeSH Prohlížeč
• toll-like receptor 2 MeSH
• toll-like receptor 4 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   patogenita   MeSH
• gastrointestinální trakt mikrobiologie   MeSH
• gnotobiologické modely MeSH
• infekce vyvolané Escherichia coli imunologie   mikrobiologie   patologie   MeSH
• kolitida chemicky indukované   imunologie   mikrobiologie   patologie   MeSH
• myši inbrední BALB C MeSH
• myši SCID MeSH
• myši MeSH
• síran dextranu MeSH
• střevní sliznice imunologie   mikrobiologie   patologie   MeSH
• zánět imunologie   mikrobiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• síran dextranu MeSH