scholarly journals Identification of Urinary Biomarkers of Colon Inflammation in IL10-/-Mice Using Short-Column LCMS Metabolomics

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Don Otter ◽  
Mingshu Cao ◽  
Hui-Ming Lin ◽  
Karl Fraser ◽  
Shelley Edmunds ◽  
...  
Keyword(s):  
Intestinal Microflora ◽  
Interleukin 10 ◽  
Xanthurenic Acid ◽  
Wild Type ◽  
Mass Spectral ◽  
Short Column ◽  
Colon Inflammation ◽  
Metabolite Concentrations ◽  
Specific Pathogen ◽  
Unidentified Metabolite

The interleukin-10-deficient (IL10-/-) mouse develops colon inflammation in response to normal intestinal microflora and has been used as a model of Crohn's disease. Short-Column LCMS metabolite profiling of urine from IL10-/-and wild-type (WT) mice was used, in two independent experiments, to identify mass spectral ions differing in intensity between these two genotypes. Three differential metabolites were identified as xanthurenic acid and as the glucuronides of xanthurenic acid and of α-CEHC (2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman). The significance of several differential metabolites as potential biomarkers of colon inflammation was evaluated in an experiment which compared metabolite concentrations in IL10-/-and WT mice housed, either under conventional conditions and dosed with intestinal microflora, or maintained under specific pathogen-free (SPF) conditions. Concentrations of xanthurenic acid, α-CEHC glucuronide, and an unidentified metabolitem/z495-/497+were associated with the degree of inflammation in IL10-/-mice and may prove useful as biomarkers of colon inflammation.

scholarly journals Comparison of Salmonellaenterica Serovar Typhimurium Colitis in Germfree Mice and Mice Pretreated with Streptomycin

2005 ◽  
Vol 73 (6) ◽  
pp. 3228-3241 ◽  
Author(s):  
Bärbel Stecher ◽  
Andrew J. Macpherson ◽  
Siegfried Hapfelmeier ◽  
Marcus Kremer ◽  
Thomas Stallmach ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Intestinal Microflora ◽  
Specific Pathogen Free ◽  
Colonization Resistance ◽  
Pathogenetic Mechanisms ◽  
Colon Inflammation ◽  
Physiological Properties ◽  
Infection Models ◽  
Serovar Typhimurium ◽  
Specific Pathogen

ABSTRACT Salmonella enterica subspecies 1 serovar Typhimurium is a common cause of bacterial enterocolitis. Mice are generally protected from Salmonella serovar Typhimurium colonization and enterocolitis by their resident intestinal microflora. This phenomenon is called “colonization resistance” (CR). Two murine Salmonella serovar Typhimurium infection models are based on the neutralization of CR: (i) in specific-pathogen-free mice pretreated with streptomycin (StrSPF mice) antibiotics disrupt the intestinal microflora; and (ii) germfree (GF) mice are raised without any intestinal microflora, but their intestines show distinct physiologic and immunologic characteristics. It has been unclear whether the same pathogenetic mechanisms trigger Salmonella serovar Typhimurium colitis in GF and StrSPF mice. In this study, we compared the two colitis models. In both of the models Salmonella serovar Typhimurium efficiently colonized the large intestine and triggered cecum and colon inflammation starting 8 h postinfection. The type III secretion system encoded in Salmonella pathogenicity island 1 was essential in both disease models. Thus, Salmonella serovar Typhimurium colitis is triggered by similar pathogenetic mechanisms in StrSPF and GF mice. This is remarkable considering the distinct physiological properties of the GF mouse gut. One obvious difference was more pronounced damage and reduced regenerative response of the cecal epithelium in GF mice. Overall, StrSPF mice and GF mice provide similar but not identical models for Salmonella serovar Typhimurium colitis.

scholarly journals Characteristic Intestinal Microflora of Specific Pathogen-Free Mice Bred in Two Different Colonies and their Influence on Postnatal Murine Immunocyte Profiles

2005 ◽  
Vol 54 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Taizo NAGURA ◽  
Satoshi HACHIMURA ◽  
Shuichi KAMINOGAWA ◽  
Tsutomu ARITSUKA ◽  
Kikuji ITOH
Keyword(s):  
Intestinal Microflora ◽  
Specific Pathogen Free ◽  
Specific Pathogen

scholarly journals Failure of Surface Ring Mutant Strains of Helicobacter mustelae To Persistently Infect the Ferret Stomach

2003 ◽  
Vol 71 (5) ◽  
pp. 2350-2355 ◽  
Author(s):  
M. M. Patterson ◽  
P. W. O'Toole ◽  
N. T. Forester ◽  
B. Noonan ◽  
T. J. Trust ◽  
...  
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Gastric Body ◽  
Wild Type ◽  
Significant Difference ◽  
Specific Pathogen ◽  
Ring Structures ◽  
H Pylori ◽  
Successful Colonization ◽  
Persistently Infect

ABSTRACT Helicobacter mustelae, the gastric pathogen of ferrets, produces an array of surface ring structures which have not been described for any other member of the genus Helicobacter, including H. pylori. The unique ring structures are composed of a protein named Hsr. To investigate whether the Hsr rings are important for colonization of the ferret stomach, ferrets specific pathogen free for H. mustelae were inoculated with an Hsr-deficient mutant strain or the wild-type H. mustelae strain. Quantitative cultures from antral biopsy specimens obtained at 3, 6, and 9 weeks postinoculation demonstrated no significant difference in the levels of bacteria in the ferrets that received the Hsr-negative strain and the ferrets infected with the parent strain. However, when the ferrets were biopsied at 12 and 15 weeks and necropsied at 18 weeks after infection, the levels of bacteria of the Hsr-negative strain in the stomach antrum were significantly reduced. This decline contrasted the robust antral colonization by the wild-type strain. The Hsr-negative strain did not efficiently colonize the gastric body of the study ferrets. Histological examination at 18 weeks postinoculation revealed minimal gastric inflammation in the animals that received the mutant H. mustelae strain, a finding consistent with its waning infection status, whereas lesions characteristic of helicobacter infection were present in ferrets infected with the wild-type strain. Scant colonization by the Hsr-negative H. mustelae strain at the end of the 18-week study, despite initial successful colonization, indicates an inability of the mutant to persist, perhaps due to a specific host response.

scholarly journals Effect of Massa Medicata Fermentata on the Gut Microbiota of Dyspepsia Mice Based on 16S rRNA Technique

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiaorui Zhang ◽  
Hongling Zhang ◽  
Qinwan Huang ◽  
Jilin Sun ◽  
Renchuan Yao ◽  
...  
Keyword(s):  
16S Rrna ◽  
Intestinal Microflora ◽  
Intestinal Flora ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Blank Group ◽  
Intestinal Microorganisms ◽  
Specific Pathogen ◽  
Rrna Gene Sequencing ◽  
Aseptic Conditions

Massa Medicata Fermentata (MMF) is a traditional Chinese medicine (TCM) for treating indigestion and its related disorders. This study analyzes the effect of MMF on intestinal microorganisms in dyspepsia mice based on 16S rRNA technology. We take a dyspepsia model caused by a high-protein, high-calorie, high-fat diet. The 60 specific-pathogen free Kunming (SPF KM) mice were randomly divided into a model group n=12, an MMF group (LSQ group, n=12), a Jianweixiaoshi group (JWXS group, n=12), a domperidone group (DP group, n=12), and a blank group n=12. On the seventh day of administration, mice were fasted and deprived of water. After 24 h, take the second feces of stress defecation in mice under strict aseptic conditions and quickly transfer them to a sterile cryotube. This study comprehensively evaluates the α-diversity, β-diversity, flora abundance and composition of each group of miceʼs intestinal microorganisms, and their correlation with functional dyspepsia based on the 16S rRNA gene sequencing technology. After modeling, some dyspepsia reactions, proximal gastric relaxation reduction, and intestinal microflora changes were noted. Dyspepsia mice showed dyspepsia reactions and proximal gastric relaxation reduction, characterized by a significant decrease of contents of gastrin P<0.01 and cholinesterase P<0.01. MMF can improve dyspepsia symptoms and promote proximal gastric relaxation. Significant intestinal flora disorders were found in dyspepsia mice, including downregulation of Bacteroidetes, Lactobacillus, and Prevotellaceae and upregulation of Proteobacteria, Verrucomicrobia, Epsilonbacteraeota, Firmicutes, Lachnospiraceae NK4A136 group, and Lachnospiraceae. MMF could alleviate intestinal microflora disturbance, and the regulation effect of MMF on Bacteroidetes, Verrucomicrobia, and Epsilonbacteraeota was more reliable than that of Jianweixiaoshi tables and domperidone. The intestinal microflora may be correlated with the promoted digestion of MMF.

scholarly journals Interleukin 10- and Fcγ Receptor-Deficient Mice Resolve Leishmania mexicana Lesions

2005 ◽  
Vol 73 (4) ◽  
pp. 2101-2108 ◽  
Author(s):  
Laurence U. Buxbaum ◽  
Phillip Scott
Keyword(s):  
Chronic Disease ◽  
Interleukin 10 ◽  
Delayed Type Hypersensitivity ◽  
Leishmania Mexicana ◽  
Wild Type ◽  
Enhanced Resistance ◽  
Lymph Node Cells ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT Infection of C57BL/6 (B6) mice with Leishmania mexicana is associated with a minimal immune response and chronic disease. Here we show that B6 interleukin 10−/− (IL-10−/−) mice resolve their lesions and exhibit increased gamma interferon (IFN-γ), nitric oxide production, and delayed-type hypersensitivity. This enhanced resistance was dependent upon IL-12p40, since treatment of L. mexicana-infected IL-10−/− mice with anti-IL-12p40 monoclonal antibody abrogated healing. Antibody-opsonized L. mexicana induced IL-10 production by B6 macrophages in vitro, implicating antibody binding to Fc receptors as a mechanism involved in IL-10 production in this infection. Furthermore, B6 FcRγ−/− mice resolve L. mexicana lesions, and lymph node cells from these mice produced less IL-10 and more IFN-γ than cells from infected wild-type mice. These data demonstrate that removal of IL-10 or FcγR leads to resolution of L. mexicana disease and support a model in which ligation of FcγR by L. mexicana-bound immunoglobulin G promotes IL-10 production, leading to chronic disease.

scholarly journals Caspase-11 attenuates gastrointestinal inflammation and experimental colitis pathogenesis

2015 ◽  
Vol 308 (2) ◽  
pp. G139-G150 ◽  
Author(s):  
Tere M. Williams ◽  
Rachel A. Leeth ◽  
Daniel E. Rothschild ◽  
Dylan K. McDaniel ◽  
Sheryl L. Coutermarsh-Ott ◽  
...  
Keyword(s):  
Critical Factor ◽  
Experimental Colitis ◽  
Wild Type ◽  
Colonic Injury ◽  
Caspase 1 ◽  
Colon Inflammation ◽  
Cytokine Analysis ◽  
Relapsing Remitting ◽  
Inflammatory Bowel ◽  
And Function

Nucleotide-binding domain and leucine-rich repeat containing protein inflammasome formation plays an essential role in modulating immune system homeostasis in the gut. Recently, a caspase-11 noncanonical inflammasome has been characterized and appears to modulate many biological functions that were previously considered to be solely dependent on caspase-1 and the canonical inflammasome. To better elucidate the function of this noncanonical inflammasome during inflammatory bowel disease, experimental colitis was induced in wild-type and Casp11 −/− mice utilizing dextran sulfate sodium (DSS). Here, we report that caspase-11 attenuates acute experimental colitis pathogenesis. Casp11 −/− mice showed significantly increased morbidity and colon inflammation following DSS exposure. Subsequent cytokine analysis revealed that IL-1β and IL-18 levels in the colon were significantly reduced in the Casp11 −/− mice compared with the wild-type animals. Additional mechanistic studies utilizing IL-1β and IL-18 reconstitution revealed that Casp11 −/− hypersensitivity was associated with the loss of both of these cytokines. Bone marrow reconstitution experiments further revealed that caspase-11 gene expression and function in both hematopoietic- and nonhematopoietic-derived cells contribute to disease attenuation. Interestingly, unlike caspase-1, caspase-11 does not appear to influence relapsing remitting disease progression or the development of colitis-associated tumorigenesis. Together, these data identify caspase-11 as a critical factor protecting the host during acute DSS-induced colonic injury and inflammation but not during chronic inflammation and tumorigenesis.

scholarly journals Phenotypic Switching in Cryptococcus neoformans Contributes to Virulence by Changing the Immunological Host Response

2008 ◽  
Vol 76 (9) ◽  
pp. 4322-4331 ◽  
Author(s):  
Abraham Guerrero ◽  
Bettina C. Fries
Keyword(s):  
Inflammatory Response ◽  
Cryptococcus Neoformans ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Interleukin 10 ◽  
Host Responses ◽  
Phenotypic Switching ◽  
Wild Type ◽  
Necrosis Factor Alpha

ABSTRACT Cryptococcus neoformans is an encapsulated opportunistic organism that can undergo phenotypic switching. In this process, the parent smooth colony (SM) switches to a more virulent mucoid colony (MC) variant. The host responses mounted against the SM and MC variants differ, and lower tissue interleukin 10 (IL-10) levels are consistently observed in lungs of MC-infected C57BL/6 and BALB/c mice. This suggested different roles of this cytokine in SM and MC infections. The objective of this study was to compare survival rates and characterize the host responses of SM- and MC-infected IL-10-depleted (IL-10−/−) mice, which exhibit a Th1-polarized immune response and are considered resistant hosts. As expected, SM-infected IL-10−/− mice survived longer than wild-type mice, whereas MC-infected IL-10−/− mice did not exhibit a survival benefit. Consistent with this observation, we demonstrated marked differences in the inflammatory responses of SM- and MC-infected IL-10−/− and wild-type mice. This included a more Th1-polarized inflammatory response with enhanced recruitment of macrophages and natural killer and CD8 cells in MC- than in SM-infected IL-10−/− and wild-type mice. In contrast, both SM-infected IL-10−/− and wild-type mice exhibited higher recruitment of CD4 cells, consistent with enhanced survival and differences in recruitment and Th1/Th2 polarization. Lung tissue levels of IL-21, IL-6, IL-4, transforming growth factor beta, IL-12, and gamma interferon were higher in MC-infected IL-10−/− and wild-type mice than in SM-infected mice, whereas tumor necrosis factor alpha levels were higher in SM-infected IL-10−/− mice. In conclusion, the MC variant elicits an excessive inflammatory response in a Th1-polarized host environment, and therefore, the outcome is negatively affected by the absence of IL-10.

scholarly journals Changes in colon gene expression associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species

2010 ◽  
Vol 11 (1) ◽  
pp. 39 ◽  
Author(s):  
Matthew PG Barnett ◽  
Warren C McNabb ◽  
Adrian L Cookson ◽  
Shuotun Zhu ◽  
Marcus Davy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interleukin 10 ◽  
Enterococcus Species ◽  
Colon Inflammation ◽  
Deficient Mice

scholarly journals Functional regions of the mouse interleukin-10 receptor cytoplasmic domain.

1995 ◽  
Vol 15 (9) ◽  
pp. 5043-5053 ◽  
Author(s):  
A S Ho ◽  
S H Wei ◽  
A L Mui ◽  
A Miyajima ◽  
K W Moore
Keyword(s):  
Transmembrane Domain ◽  
Cytoplasmic Domain ◽  
Interleukin 10 ◽  
Proliferation Assay ◽  
Wild Type ◽  
Cell Surface Antigens ◽  
Functional Regions ◽  
Heat Stable ◽  
C Terminus ◽  
Heat Stable Antigen

The functions of wild-type and mutant mouse interleukin-10 receptors (mIL-10R) expressed in murine Ba/F3 cells were studied. As observed previously, IL-10 stimulates proliferation of IL-10R-expressing Ba/F3 cells. Accumulation of viable cells in the proliferation assay is to a significant extent balanced by concomitant cell death. Moreover, growth in IL-10 also induces a previously unrecognized response, differentiation of the cells, as evidenced both by formation of large clusters of cells in cultures with IL-10 and by induction or enhancement of expression of several cell surface antigens, including CD32/16, CD2, LECAM-1 (v-selectin), and heat-stable antigen. Two distinct functional regions near the C terminus of the mIL-10R cytoplasmic domain which mediate proliferation were identified; one of these regions also mediates the differentiation response. A third region proximal to the transmembrane domain was identified; removal of this region renders the cell 10- to 100-fold more sensitive to IL-10 in the proliferation assay. In cells expressing both wild-type and mutant IL-10R, stimulation with IL-10 leads to tyrosine phosphorylation of the kinases JAK1 and TYK2 but not JAK2 or JAK3 under the conditions tested.

scholarly journals Organ Correlation with Tryptophan Metabolism Obtained by Analyses of TDO-KO and QPRT-KO Mice

2016 ◽  
Vol 9 ◽  
pp. IJTR.S37984 ◽  
Author(s):  
Katsumi Shibata ◽  
Tsutomu Fukuwatari
Keyword(s):  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Conversion Ratio ◽  
Tryptophan Metabolism ◽  
Limiting Factors ◽  
Xanthurenic Acid ◽  
Wild Type ◽  
Organ Specific ◽  
Hydroxyanthranilic Acid ◽  
Rate Limiting

The aim of this article is to report the organ-specific correlation with tryptophan (Trp) metabolism obtained by analyses of tryptophan 2,3-dioxygenase knockout (TDO-KO) and quinolinic acid phosphoribosyltransferase knockout (QPRT-KO) mice models. We found that TDO-KO mice could biosynthesize the necessary amount of nicotinamide (Nam) from Trp, resulting in the production of key intermediate, 3-hydroxyanthranilic acid. Upstream metabolites, such as kynurenic acid and xanthurenic acid, in the urine were originated from nonhepatic tissues, and not from the liver. In QPRT-KO mice, the Trp to quinolinic acid conversion ratio was 6%; this value was higher than expected. Furthermore, we found that QPRT activity in hetero mice was half of that in wild-type (WT) mice. Urine quinolinic acid levels remain unchanged in both hetero and WT mice, and the conversion ratio of Trp to Nam was also unaffected. Collectively, these findings show that QPRT was not the rate-limiting enzyme in the conversion. In conclusion, the limiting factors in the conversion of Trp to Nam are the substrate amounts of 3-hydroxyanthranilic acid and activity of 3-hydroxyanthranilic acid 3,4-dioxygenase in the liver.

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