Ginger and its component ameliorated trinitrobenzene sulfonic acid-induced colitis in mice via modulation of nuclear factor-κB activity and interleukin-1β signaling pathway
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE37677 | GEO | 2015/04/28
SECONDARY ACCESSION(S): PRJNA163229
REPOSITORIES: GEO
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Project description:Colitis is the common pathological lesion of inflammatory bowel diseases, the major chronic inflammatory diseases of intestinal tracts in humans. In this study, we investigated the therapeutic effects of ginger extract and its component zingerone in mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Mice were administered with TNBS and/or various amounts of ginger and zingerone by an intrarectal route. The severity of colitis was evaluated by colonic weight/length ratio, macroscopic lesion, and histological examination. The mechanisms of ginger and zingerone were further elucidated by DNA microarray, ex vivo imaging, and immunohistochemical staining. Our data showed that treatment with ginger extract and zingerone ameliorated TNBS-induced colonic inflammation and injury in a dose-dependent manner. Pathway analysis of ginger- and zingerone-regulated gene expression profiles showed that ginger and zingerone significantly regulated cytokine-related pathways. Network analysis showed that nuclear factor-κB (NF-κB) and interleukin-1β (IL-1β) were key molecules involved in the expression of ginger- and zingerone-affected genes. Ex vivo imaging and immunohistochemical staining further verified that ginger and zingerone suppressed TNBS-induced NF-κB activation and decreased the NF-κB and IL-1β protein levels in the colon. In conclusion, our data showed that ginger improved the TNBS-induced colitis in mice via modulation of NF-κB activity and IL-1β signaling pathway. Moreover, zingerone might be the active component of ginger responsible for the amelioration of colitis induced by TNBS. A total of 24 mice was randomly divided into four groups of six mice: mock, mice were given with 0.1 ml of 50% ethanol; TNBS, mice were given with 250 mg/kg TNBS in 0.1 ml of 50% ethanol; TNBS/ginger, mice were administered with mixtures containing 250 mg/kg TNBS and various amounts of ginger extract in 0.1 ml of 50% ethanol; TNBS/zingerone, mice were given with mixtures containing 250 mg/kg TNBS and various amounts of zingerone in 0.1 ml of 50% ethanol. Mice were sacrificed seven days later for histochemical staining, RNA extraction, and ex vivo imaging.
2015-04-28 | E-GEOD-37677 | biostudies-arrayexpress
Project description:Inflammatory bowel disease is a chronic colonic inflammation that displays symptoms like diarrhea and weight loss. Acupuncture has been widely accepted by Western countries for the treatment of pain. In this study, we analyzed the efficacy and mechanism of electroacupuncture (EA) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in mice. Mice were intrarectally administered 250 mg/kg TNBS and electroacupunctured at Quze (PC3) and Neiguan (PC6) acupoints, which have been applied for gastrointestinal disorders. Gene expression profiles in colons and spleens were analyzed by microarray for the elucidation of mechanism of EA. Our data showed that EA at PC3 and PC6 improved macroscopic and microscopic features of colitis, and the improvement displayed a frequency-dependent manner. Administration of TNBS upregulated the expression of most cytokine genes in colons, while EA downregulated the expression of TNBS-induced cytokine genes. Pathway analysis showed that EA significantly affected inflammatory pathways in colons and immunity-associated pathway in spleens. Immunohistochemical staining further showed that EA decreased the expression of interleukin-1β and nuclear factor-κB. In conclusion, this is the first study reporting the global gene expression profiles of EA on TNBS-induced colitis. Our findings suggested that inflammatory and immunity pathways were involved in the anti-inflammatory mechanism of EA on colitis induced by TNBS.
2014-09-02 | GSE57771 | GEO
Project description:Urinary tract infection (UTI) is a common problem in long-term care facilities. Roselle (Hibiscus sabdariffa Linn.) has been used in fold medicine as an anti-inflammatory agent. In this study, we surveyed the effect of roselle drink on the prevention of UTI in long-term care facilities and analyzed the anti-inflammatory potential of roselle on lipopolysaccharide (LPS)-induced renal inflammation. By survey questionnaires, we found that roselle drink was the most commonly used treatment for the routine care of residents. In addition, taking roselle drink in residents with urinary catheters reduced the incidence of UTI by 36%. Roselle suppressed LPS-induced nuclear factor-κB (NF-κB) activation in cells in a dose-dependent manner, and the maximal inhibition (73.75±4.11%) was observed at 100 μg/ml roselle drink. Roselle also suppressed LPS-induced interleukin-1β (IL-1β) production in mice. Gene expression profile of roselle in kidney showed that roselle downregulated the expression of inflammatory genes, and NF-κB was the main transcription factor involved in the regulation of roselle-regulated gene expression. Immunohistochemical staining further showed that roselle inhibited LPS-induced NF-κB activation and inflammatory cell infiltration in kidney. In conclusion, our findings suggested that roselle drink might be a potent benefit herbal supplement for UTI. Moreover, roselle ameliorated LPS-induced renal inflammation via regulating inflammatory gene expression and NF-κB pathway.
2017-08-21 | GSE73939 | GEO
Project description:Inflammatory bowel disease is a chronic colonic inflammation that displays symptoms like diarrhea and weight loss. Acupuncture has been widely accepted by Western countries for the treatment of pain. In this study, we analyzed the efficacy and mechanism of electroacupuncture (EA) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in mice. Mice were intrarectally administered 250 mg/kg TNBS and electroacupunctured at Quze (PC3) and Neiguan (PC6) acupoints, which have been applied for gastrointestinal disorders. Gene expression profiles in colons and spleens were analyzed by microarray for the elucidation of mechanism of EA. Our data showed that EA at PC3 and PC6 improved macroscopic and microscopic features of colitis, and the improvement displayed a frequency-dependent manner. Administration of TNBS upregulated the expression of most cytokine genes in colons, while EA downregulated the expression of TNBS-induced cytokine genes. Pathway analysis showed that EA significantly affected inflammatory pathways in colons and immunity-associated pathway in spleens. Immunohistochemical staining further showed that EA decreased the expression of interleukin-1? and nuclear factor-?B. In conclusion, this is the first study reporting the global gene expression profiles of EA on TNBS-induced colitis. Our findings suggested that inflammatory and immunity pathways were involved in the anti-inflammatory mechanism of EA on colitis induced by TNBS. In this study, we analyzed the efficacy and mechanism of electroacupuncture (EA) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in mice. Mice were intrarectally administered 250 mg/kg TNBS and electroacupunctured at Quze (PC3) and Neiguan (PC6) acupoints, which have been applied for gastrointestinal disorders. Gene expression profiles in colons and spleens were analyzed by microarray for the elucidation of mechanism of EA.
2014-09-02 | E-GEOD-57771 | biostudies-arrayexpress
Project description:The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 does not induce Il1b expression in CD4+ T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1β processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1β expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with Pneumonia Virus of Mice. These results demonstrate lineage-restricted IL-21-induced IL-1β via a non-canonical pathway and provide evidence for its importance in vivo.
2015-07-07 | GSE61677 | GEO
Project description:Gastric mucosa responds to the pathogen Helicobacter pylori (H. pylori) by producing and release of pro-inflammatory cytokines that activate the innate immune system mainly through activation of the transcription factor NF-κB. Although NF-κB signaling is well studied for many possible inducers, induction by H. pylori remains poorly understood. Here, we performed a high-throughput genome-wide RNAi screen for genes influencing H. pylori-induced NF-κB activation. In comparison to TNFα or IL‐1β NF‐κB signaling, we identified 21 proteins unique necessary for H. pylori NF-κB pathway and 24 factors that inhibited the activation. Furthermore, we present here the R/Bioconductor package Nested Effect Model for systematic use in high-throughput screens to classify newly identified factors. We identified alpha kinase 1 (ALPK1) as particular important for the H. pylori NF‐κB pathway without affecting TNFα or IL‐1β signaling. ALPK1 silencing inhibits activity of TAK1 and the IκB kinases (IKKs), degradation of the NF‐κB inhibitor IκBα, nuclear translocation of the NF‐κB subunit p65, and transcription of the NF‐κB target genes, e.g. IL‐8. Thus, we identify ALPK1 as a novel inflammatory regulator functioning particularly in the NF‐κB signaling network activated by H. pylori.
2019-09-02 | GSE89613 | GEO
Project description:To test the efficacy of TNFR-Fc and anti-TWEAK mAb treatment alone and in combination Tumor necrosis factor (TNF)-alpha is a major effector in various inflammatory conditions. TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily that promotes inflammatory tissue damage through its receptor, FGF-inducible molecule 14 (Fn14). Since both TWEAK and TNF-alpha have been shown to mediate pathological responses through inter-dependent or independent pathways by in vitro, the potential interplay of these pathways was investigated in a mouse colitis model. Acute colitis was induced by rectal injection of trinitrobenzene sulfonic acid (TNBS), with administration of control IgG, TNF receptor (TNFR)-Ig chimeric protein, anti-TWEAK monoclonal antibody, or the combination of TNFR-Ig and anti-TWEAK antibody. On day 4, disease severity was evaluated and gene expression profiling was analyzed using whole colon tissue. Levels of transcript of TWEAK, Fn14 and NF-kB-related molecules were measured in purified colon epithelial cells (ECs). NF-kB activation was investigated with Western blot and immunohistochemical analysis. As a result, activation of the canonical, but not noncanonical NF-kB pathway was the hallmark of inflammatory responses in this model. Inflammation induced upregulation of Fn14 only in ECs but not in other cell types. Combination treatment of TNFR-Ig and anti-TWEAK antibody synergistically reduced disease severity in comparison with the control antibody or single agent treatment. Gene expression profile of the colon indicated downregulation of canonical NF-kB pathway with combination treatment. In conclusion, synergistic activation of canonical NF-kB by TWEAK and TNF-alpha is critical for the induction of inflammatory tissue damage in acute inflammation. TNBS colitis was induced by intrarectal administration of a 2 % solution of TNBS in phosphate-buffered saline (PBS): ethanol (1:1). For acute inflammatory responses, 70 M-NM-<g/g body weight of TNBS was given on day 0 and animals sacrificed on day 4. One hour prior to administration of TNBS, groups of mice were injected i.p. with the control IgG2a mAb (anti-human CD20) (10 mg/kg), TNFR-Ig (0.3 mg/kg), anti-TWEAK (mP2D10, 10 mg/kg), the combination of TNFR-Fc (0.3 mg/kg) and anti-TWEAK mP2D10 (10 mg/kg), or were untreated. For single agent and combination treatments groups, 0.3 mg/kg TNFR-Ig was employed, since 1 mg/kg of TNFR-Ig markedly ameliorated TNBS colitis but 0.3 mg/kg was much less effective as monitored by the effect on colon length and body weight. Colon tissue was rolled and snap-frozen in liquid nitrogen. Specimens for RNA extraction were cut from the frozen rolled colon. A set of experiments using 5-8 mice for each experimental group was performed twice, labelled 7 and 10 in the CEL files. Total number of mice for each experimental condition was as follows; untreated TNBS colitis group, 8; control antibody, 15; TNFR-Ig, 12; anti-TWEAK mAb, 14; combination of TNFR-Ig and anti-TWEAK mAb, 15.
2014-05-30 | E-GEOD-53835 | biostudies-arrayexpress
Project description:Analysis of mechano-regulation of tenocyte metabolism at gene expression level. The hypothesis tested in the present study was that cyclic tensile strain influence the balance of anabolism/catabolism of tenocytes. Forkhead box O (FoxO) proteins are a family of transcription factors implicated in many biological processes including immune regulation. In this study, we found that mice null for Foxo4, a member of the FoxO family, are more susceptible to 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis than wild type controls. To understand the mechanism of elevated colitis susceptibility and the nature of the TNBS-induced colitis in Foxo4-null mice, we performed microarray analysis with mucosal cDNA samples from large intestines of untreated, ethanol and TNBS-treated wild type and Foxo4 KO mice. Unexpectedly, we found that cytokine CCL5, CXCL9, TNFalpha, and IFNgamma were already significantly upregulated in untreated Foxo4-null mice compared to WT controls despite lack of visible colonic phenotypes. Consistent with the exacerbated inflammatory phenotype in TNBS-treated Foxo4 KO mice, expressions of these inflammatory cytokines are further upregulated after TNBS-treatment. In addition, we observed many more inflammatory cytokines that were upregulated in TNBS-treated Foxo4 KO mice, including chemokines (CCL3, 4, 7, 8, 11, 12, 21b and CXCL1, 12, 14), chemokine receptors (CCR7, CCRl2, 8,CXC3CR1), cytokines (IL-1, IL-6, IL-11, IFI205), and cytokine receptors (TNFrsf). Interestingly, many of the anti-bacterial peptides were also up-regulated in TNBS treated Foxo4 KO mice including defensin related cryptdin (Defcr3,5,6, 9,13) and Defcr related sequence (Defcr-cr1,2,10,12). Up-regulation of basal level of IFNgamma, TNFalpha, CCL5, and CXCL9 expression in Foxo4 KO mice is specific to colonic tissues, as no significant difference of these gene transcript levels between wild type and Foxo4 KO mice was observed in other tissues including thymus . IFNgamma, TNFalpha, and IL-1ï¢which are upregulated in TNBS-treated Foxo4 KO mice, are Th1 type cytokines. This is consistent with the Th1 inflammatory phenotype observed in TNBS-treated Foxo4-KO mice. We also tested whether the expression of Th2 cytokines (IL-4, IL-5, and IL-13) is altered in TNBS-treated WT and Foxo4-null mice in comparison to ethanol-treated mice and observed no significant differences suggesting that the TNBS-induced colitis in Foxo4-null FVB mice is predominantly Th1 in nature. Colonic mucosal tissues from five mice per treatment group (untreated, two days after ethanol or TNBS-treatment) were pooled. Total RNA obtained from colon mucosa isolated tendon fascicles subjected to 1 or 24 hours in vitro cyclic tensile strain compared to unstrained control fascicles.
2010-05-28 | E-GEOD-16033 | biostudies-arrayexpress
Project description:Analysis of mechano-regulation of tenocyte metabolism at gene expression level. The hypothesis tested in the present study was that cyclic tensile strain influence the balance of anabolism/catabolism of tenocytes. Forkhead box O (FoxO) proteins are a family of transcription factors implicated in many biological processes including immune regulation. In this study, we found that mice null for Foxo4, a member of the FoxO family, are more susceptible to 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis than wild type controls. To understand the mechanism of elevated colitis susceptibility and the nature of the TNBS-induced colitis in Foxo4-null mice, we performed microarray analysis with mucosal cDNA samples from large intestines of untreated, ethanol and TNBS-treated wild type and Foxo4 KO mice. Unexpectedly, we found that cytokine CCL5, CXCL9, TNFalpha, and IFNgamma were already significantly upregulated in untreated Foxo4-null mice compared to WT controls despite lack of visible colonic phenotypes. Consistent with the exacerbated inflammatory phenotype in TNBS-treated Foxo4 KO mice, expressions of these inflammatory cytokines are further upregulated after TNBS-treatment. In addition, we observed many more inflammatory cytokines that were upregulated in TNBS-treated Foxo4 KO mice, including chemokines (CCL3, 4, 7, 8, 11, 12, 21b and CXCL1, 12, 14), chemokine receptors (CCR7, CCRl2, 8,CXC3CR1), cytokines (IL-1, IL-6, IL-11, IFI205), and cytokine receptors (TNFrsf). Interestingly, many of the anti-bacterial peptides were also up-regulated in TNBS treated Foxo4 KO mice including defensin related cryptdin (Defcr3,5,6, 9,13) and Defcr related sequence (Defcr-cr1,2,10,12). Up-regulation of basal level of IFNgamma, TNFalpha, CCL5, and CXCL9 expression in Foxo4 KO mice is specific to colonic tissues, as no significant difference of these gene transcript levels between wild type and Foxo4 KO mice was observed in other tissues including thymus. IFNgamma, TNFalpha, and IL-1beta, which are upregulated in TNBS-treated Foxo4 KO mice, are Th1 type cytokines. This is consistent with the Th1 inflammatory phenotype observed in TNBS-treated Foxo4-KO mice. We also tested whether the expression of Th2 cytokines (IL-4, IL-5, and IL-13) is altered in TNBS-treated WT and Foxo4-null mice in comparison to ethanol-treated mice and observed no significant differences suggesting that the TNBS-induced colitis in Foxo4-null FVB mice is predominantly Th1 in nature.
2010-05-12 | GSE16033 | GEO
Project description:Genipin is a natural blue colorant in food industry. Inflammation is correlated with human disorders, and nuclear factor-κB (NF-κB) is the critical molecule involved in inflammation. In this study, the anti-inflammatory effect of genipin on the lipopolysaccharide (LPS)-induced acute systemic inflammation in mice was evaluated by NF-κB bioluminescence-guided transcriptomic analysis. Transgenic mice carrying the NF-κB-driven luciferase genes were administered intraperitoneally with LPS and various amounts of genipin. Bioluminescent imaging showed that genipin significantly suppressed LPS-induced NF-κB-dependent luminescence in vivo. The suppression of LPS-induced acute inflammation by genipin was further evidenced by the reductions of cytokine levels in sera and organs. Microarray analysis of these organs showed that the transcripts of 79 genes were differentially expressed in both LPS and LPS/genipin groups, and one third of these genes belonged to chemokine ligand, chemokine receptor, and interferon (IFN)-induced protein genes. Moreover, network analysis showed that NF-κB played a critical role in the regulation of genipin-affected gene expression. In conclusion, we newly identified that genipin exhibited anti-inflammatory effects in a model of LPSinduced acute systemic inflammation via downregulation of chemokine ligand, chemokine receptor, and IFN-induced protein productions. A total of 25 transgenic mice (female, 6 to 8 weeks old) were randomly divided into five groups of five mice: (1) mock, no treatment; (2) LPS (4 mg/kg), (3) LPS plus genipin (1 mg/kg), (4) LPS plus genipin (10 mg/kg), and (5) LPS plus genipin (100 mg/kg). Mice were challenged intraperitoneally with LPS and then with genipin 10 min later. Four hours later, mice were imaged for the luciferase activity, and subsequently sacrificed for ex vivo imaging, RNA extraction, and immunohistochemical staining.
2012-02-25 | E-GEOD-35934 | biostudies-arrayexpress