The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.

• MeSH
• idiopatické střevní záněty metabolismus   patologie   MeSH
• lidé MeSH
• monocyty metabolismus   účinky léků   MeSH
• pohyb buněk účinky léků   MeSH
• serotonin * farmakologie   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• střevní sliznice * metabolismus   účinky léků   patologie   imunologie   MeSH
• TNF-alfa * MeSH
• zánět * metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• serotonin * MeSH
• TNF-alfa * 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