Infliximab therapy decreases the levels of TNF-α and IFN-γ mRNA in colonic mucosa of ulcerative colitis

2009 ◽  
Vol 44 (6) ◽  
pp. 727-735 ◽  
Author(s):  
Trine Olsen ◽  
Guanglin Cui ◽  
Rasmus Goll ◽  
Anne Husebekk ◽  
Jon Florholmen
Keyword(s):  
Ulcerative Colitis ◽  
Colonic Mucosa ◽  
Infliximab Therapy ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengchao Zhang ◽  
Jiankai Fang ◽  
Zhanhong Liu ◽  
Pengbo Hou ◽  
Lijuan Cao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Human Muscle ◽  
Enzyme Linked Immunosorbent Assay ◽  
Muscle Stem Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

Pharmacological Effects of Ba-Wei-Xi-Lei Powder on Ulcerative Colitis in Rats with Enema Application

2006 ◽  
Vol 34 (03) ◽  
pp. 461-469 ◽  
Author(s):  
Duan-Yong Liu ◽  
Hai-Mei Zhao ◽  
Ning Zhao ◽  
Zeng-Ping Xin ◽  
Ai-Ping Lu
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Reaction ◽  
Peripheral Blood ◽  
Colonic Mucosa ◽  
Pharmacological Effects ◽  
Pathological Changes ◽  
Herbal Mixture ◽  
Tnf Α ◽  
Cd4 Lymphocyte ◽  
Mucosal Protein

Ba-Wei-Xi-Lei powder is a classical herbal mixture, and is widely used for the treatment of oral ulcer and ulcerative colitis. This study aimed to explore the effect of Ba-Wei-Xi-Lei powder with enema application on ulcerative colitis in rats. Ulcerative colitis was induced by immunization with rabbit's colonic mucosal protein emulsified with Completely Freund's Adjuvant. The mucosal inflammatory reaction and ulcer have been observed in the model rats. Characteristic changes of ulceractive colitis include that CD4 lymphocyte increased in peripheral blood while CD8 lymphocyte decreased; CD8 lymphocyte and TNF-α expression area increased in colonic mucosa, while CD4 lymphocyte decreased. Ba-Wei-Xi-Lei powder and sulfasalazine with enema application could alleviate the pathological changes in the model rats. The results suggest that the pharmacological effects of Ba-Wei-Xi-Lei powder on ulcerative colitis in rats are similar to the effect of sulfasalazine.

IFN-γ and TNF-α decrease serotonin transporter function and expression in Caco2 cells

2007 ◽  
Vol 292 (3) ◽  
pp. G779-G784 ◽  
Author(s):  
Kevin F. Foley ◽  
Cristen Pantano ◽  
Allison Ciolino ◽  
Gary M. Mawe
Keyword(s):  
Ulcerative Colitis ◽  
Irritable Bowel Syndrome ◽  
Conditioned Medium ◽  
Human Lymphocytes ◽  
Protein Levels ◽  
Tnf Α ◽  
Ifn Γ ◽  
5 Ht Uptake ◽  
Irritable Bowel

Recent studies have shown that mucosal serotonin (5-HT) transporter (SERT) expression is decreased in animal models of colitis, as well as in the colonic mucosa of humans with ulcerative colitis and irritable bowel syndrome. Altered SERT function or expression may underlie the altered motility, secretion, and sensation seen in these inflammatory gut disorders. In an effort to elucidate possible mediators of SERT downregulation, we treated cultured colonic epithelial cells (Caco2) with conditioned medium from activated human lymphocytes. Application of the conditioned medium caused a decrease in fluoxetine-sensitive [3H]5-HT uptake. Individual proinflammatory agents were then tested for their ability to affect uptake. Cells were treated for 48 or 72 h with PGE2 (10 μM), IFN-γ (500 ng/ml), TNF-α (50 ng/ml), IL-12 (50 ng/ml), or the nitric oxide-releasing agent S-nitrosoglutathione (GSNO; 100 μM). [3H]5-HT uptake was then measured. Neither PGE nor IL-12 had any effect on [3H]5-HT uptake, and GSNO increased uptake. However, after 3-day incubation, both TNF-α and IFN-γ elicited significant decreases in SERT function. Neither TNF-α nor IFN-γ were cytotoxic when used for this period of time and at these concentrations. These two cytokines also induced decreases in SERT mRNA and protein levels. By altering SERT expression, TNF-α and IFN-γ could contribute to the altered motility and expression seen in vivo in ulcerative colitis or irritable bowel syndrome.

scholarly journals Preventive Effect of Cardiotrophin-1 Administration before DSS-Induced Ulcerative Colitis in Mice

2019 ◽  
Vol 8 (12) ◽  
pp. 2086 ◽  
Author(s):  
Ana I. Sánchez-Garrido ◽  
Vanessa Prieto-Vicente ◽  
Víctor Blanco-Gozalo ◽  
Miguel Arévalo ◽  
Yaremi Quiros ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Course ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Tnf Α ◽  
Current Therapies ◽  
Ifn Γ ◽  
Histology And Immunohistochemistry

Ulcerative colitis is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental colitis was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Half of the mice received an i.v. dose of CT-1 (200 µg/kg) 2 h before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS administration. The severity of colitis was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF IFN-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before induction of colitis improves the clinical course, tissue damage, and inflammation in DSS-induced colitis in mice.

scholarly journals Alteration of Colonic Mucosal Permeability during Antibiotic-Induced Dysbiosis

2020 ◽  
Vol 21 (17) ◽  
pp. 6108
Author(s):  
Ying Ran ◽  
Hirokazu Fukui ◽  
Xin Xu ◽  
Xuan Wang ◽  
Nobuhiko Ebisutani ◽  
...  
Keyword(s):  
Colonic Mucosa ◽  
Polymyxin B ◽  
Mucosal Barrier ◽  
Rt Pcr ◽  
Mucosal Permeability ◽  
16S Rrna Analysis ◽  
Caco2 Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Microbiota Diversity

Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of TNF-α and/or IFN-γ was significantly increased in mice that had been administered antibiotics. TNF-α and IFN-γ stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in TNF-α and/or IFN-γ expression in mice.

scholarly journals Study on the effect of Periplaneta americana on ulcerative colitis in rats induced by 2,4,6-trinitrobenzene sulfonic acid

2020 ◽  
Vol 18 ◽  
pp. 205873922094262
Author(s):  
Yi-Hao Che ◽  
Zhi-Bin Yang ◽  
Han-Chao Zhang ◽  
Xiu-Mei Wu ◽  
Min-Zhe Sun ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Sulfonic Acid ◽  
Periplaneta Americana ◽  
Treated Group ◽  
Normal Control Group ◽  
Control Group ◽  
Trinitrobenzene Sulfonic Acid ◽  
Tnf Α ◽  
Ifn Γ ◽  
Tgf Β1

Ulcerative colitis (UC) is a chronic inflammatory disease of intestinal tract, and Periplaneta americana has been found to be effective in the treatment for UC. The purpose of the study was to investigate the therapeutic effect of Periplaneta americana extract Ento-A on UC in rats induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) and to explore its mechanism. The Sprague-Dawley (SD) rats were randomly divided into normal control group; TNBS-treated group; sulfasalazine (SASP) treated group; Ento-A low- (50 mg/kg), medium- (100 mg/kg), and high-dose (200 mg/kg) groups, respectively. The UC model of rats was induced via TNBS. Disease activity index (DAI) was used to evaluate the severity of UC in rats. The macroscopic and microscopic damages of colon were accessed by colon mucosa damage index (CMDI) and histopathological score (HS), respectively. The levels of interleukin-4 (IL-4), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in serum and the contents of myeloperoxidase (MPO), transforming growth factor-β1 (TGF-β1), and epidermal growth factor (EGF) in colonic mucosa were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the normal control group, the TNBS-treated group showed increase in DAI, CMDI, HS, IL-17, TNF-α, IFN-γ as well as MPO and decrease in the levels of IL-4, EGF, and TGF-β1. However, Ento-A-administrated groups reversed the changes in the DAI, CMDI, HS, and the cytokines caused by TNBS. The study indicates that Periplaneta americana extract Ento-A can effectively alleviate the inflammation in TNBS-induced UC of rats, and the mechanism of that may be related to restoring the balance of T helper 1 (Th1)/Th2/Th17/T regulatory (Treg) cytokines.

SER-287, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC FOR PATIENTS WITH ACTIVE MILD-TO-MODERATE ULCERATIVE COLITIS, PRODUCES REMISSION ASSOCIATED METABOLITES, REDUCES INTESTINAL EPITHELIAL IL-8 SECRETION AND PROTECTS EPITHELIAL BARRIER FUNCTION IN VITRO

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S41-S42
Author(s):  
Asunción Martínez ◽  
Divya Balasubramanian ◽  
Ambar Piña ◽  
Karen Kieser ◽  
Priyanka Narendar ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fatty Acids ◽  
Epithelial Cells ◽  
Epithelial Barrier ◽  
Epithelial Integrity ◽  
Tnf Α ◽  
Phase 1B ◽  
Ifn Γ ◽  
Culture Supernatants

Abstract Background In a Phase 1b study of mild-to-moderate ulcerative colitis (UC) (Henn et al. Gastro 2020), oral daily dosing of SER-287, a purified consortium of Firmicutes spores administered after vancomycin pre-conditioning, led to significantly higher rates of clinical remission compared to placebo (40% versus 0%, respectively; p=0.024). Engraftment, defined as SER-287 spore germination and growth of metabolically-active bacteria, was associated with remission and shifts in disease relevant microbe-associated metabolites. To better understand the mechanism underlying these favorable clinical observations, we evaluated metabolite production by SER-287 and their impact on specific inflammatory pathways and barrier epithelial integrity in vitro. Methods Three SER-287 lots and a negative control pro-inflammatory consortium including three strains isolated from UC subjects (Escherichia coli, Bifidobacterium dentium, and Streptococcus parasanguinis) were grown in vitro in a complex medium designed to mimic the nutrient composition found in the human colon. Culture supernatants were assessed for the presence of anti-inflammatory and remission associated metabolites by GC-MS or LC-MS. Anti- and pro-inflammatory activities were determined by measuring IL-8 secretion, an inflammatory cytokine whose expression is elevated in UC patients, by HT29 epithelial cells after incubation with bacterial supernatants in the presence or absence of TNF-α. Epithelial integrity was assayed by measuring FITC-dextran leakage in a trans-well culture of differentiated primary human colonic epithelial cells challenged with IFN-γ in the presence or absence of culture supernatants. Results When cultured in vitro, all SER-287 lots tested produced the anti-inflammatory short-chain fatty acids butyrate and propionate and other metabolites associated with remission in the Phase 1b trial, including tryptophan metabolites, bile acids and medium-chain fatty acids. SER-287 culture supernatants significantly reduced IL-8 secretion in TNF-α stimulated HT29 cells while the pro-inflammatory consortium increased IL-8 secretion compared to TNF-α alone (Figure 1A). SER-287 lots induced minimal IL-8 secretion in the absence of TNF-α while the pro-inflammatory consortium strongly induced IL-8 (Figure 1B). SER-287 supernatants significantly decreased IFN-γ-mediated barrier disruption, while the pro-inflammatory consortium was not protective (Figure 2). Conclusions Production of remission-associated metabolites, reduction of epithelial inflammation, and protection from epithelial barrier damage are shown to be pharmacological properties of SER-287 which may underlie the mechanism of action of this microbiome therapeutic for mild-to-moderate UC.

scholarly journals Diosmetin attenuate experimental ulcerative colitis in rats via suppression of NF-κB, TNF-α and IL-6 signalling pathways correlated with down-regulation of apoptotic events

2021 ◽  
Vol 19 ◽  
pp. 205873922110672
Author(s):  
Xiaoyan Yu ◽  
Yang Liu
Keyword(s):  
Ulcerative Colitis ◽  
Colonic Mucosa ◽  
Flavonoid Glycoside ◽  
Trinitrobenzene Sulfonic Acid ◽  
Ulcer Formation ◽  
Tnf Α ◽  
Malondialdehyde Content ◽  
Colon And Rectum ◽  
Colonic Ulceration ◽  
Experimental Ulcerative Colitis

Introduction Ulcerative colitis (UC) is a chronic inflammation of colon in which the innermost tissue of colon and rectum develops deep-rooted inflammation. Diosmetin is the aglycone of the flavonoid glycoside diosmin, commonly found in citrus fruits. Therapeutically diosmetin is indicated to demonstrate anticancer, antimicrobial, antioxidant, oestrogenic and anti-inflammatory activity. Methods In this research, we studied the action of diosmetin on TNBS (2,4,6-trinitrobenzene sulfonic acid)-induced UC in rats. Male Wister rats were anesthetised with pentobarbital and TNBS introduced by performing an enema. Diosmetin treatment was provided through oral gavage for the next 28 days. Animals were sacrificed on the 29th day and colon tissues were collected for further examinations. Results Diosmetin treatment decreased colonic ulceration dramatically and decreased the percentage of inflammation in the colonic mucosa. Depletion of the TNBS assisted of superoxide dismutase and catalase was substantially restricted, while lipid peroxidation was recorded in the colonic tissue as malondialdehyde content was also decreased. After treatment with diosmetin, the occurrence of TNF-α, IL-6and NF-κB was considerably lowered and the number of apoptotic cells observed was significantly reduced. Conclusion Taken together, these observations demonstrated the potential of diosmetin against ulcer formation and development.

Sign in / Sign up

Export Citation Format

Share Document