scholarly journals A rat model of mild intestinal inflammation induced byStaphylococcus aureusenterotoxin B

2010 ◽  
Vol 69 (3) ◽  
pp. 447-453 ◽  
Author(s):  
Anna Pérez-Bosque ◽  
Miquel Moretó
Keyword(s):  
T Lymphocytes ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Plasma Proteins ◽  
Intestinal Inflammation ◽  
Killer Cell ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Activated T Lymphocytes ◽  
Pro Inflammatory Cytokines

The epithelial barrier of the intestine and the gut-associated lymphoid tissue (GALT) protects the host against luminal pathogenic micro-organisms. This is important at weaning, when animals are exposed to infectious agents and stresses. We have developed a rat model of intestinal inflammation post weaning, based on the systemic administration ofStaphylococcus aureusenterotoxin B (SEB). Since the inflammatory response obtained is mild, the food intake pattern is not affected, which makes this model useful for studies of nutritional therapies for intestinal inflammatory disease. SEB increased T-lymphocytes in Peyer's patches and the number of activated T-lymphocytes in mesenteric lymph nodes (organized GALT). In the lamina propria, SEB increased activated T-lymphocytes as well as cytotoxic and natural killer-cell populations of the diffuse GALT. It also increased pro-inflammatory cytokines and inflammatory mediators in both Peyer's patches and mucosa. Rats given SEB had higher paracellular permeability to macromolecules, which was associated with a reduction in epithelial tightness. This model was used to examine whether dietary supplementation with spray-dried animal plasma proteins affects intestinal inflammation. Results showed that dietary plasma proteins can attenuate the mucosal immune response in both organized and diffuse GALT and that these effects are mediated by a reduction in the production of pro-inflammatory cytokines.

scholarly journals Immunomodulatory Effects of Cyperus rotundus Extract on 7,12 Dimethylbenz[a]anthracene (DMBA) Exposed BALB/c Mice

2020 ◽  
Vol 27 (1) ◽  
pp. 46-55
Author(s):  
Abu Hanifah Ramadhani ◽  
Wirdatun Nafisah ◽  
Hary Isnanto ◽  
Tri Kurniawati Sholeha ◽  
Yoga Dwi Jatmiko ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Inflammatory Cytokines ◽  
Cd8 T Cells ◽  
Graphical Analysis ◽  
Tumor Formation ◽  
Cyperus Rotundus ◽  
Carcinogenic Substance ◽  
Activated T Lymphocytes ◽  
Pro Inflammatory Cytokines

Background: The carcinogenic substance 7,12-Dimethylbenz[a]anthracene (DMBA) was commonly used to induce tumor formation in rodents. The development of tumor may trigger higher expression of pro-inflammatory cytokines, which in turn supports tumor progression. In this study, we examined the efficacy of Cyperus rotundus extract (CRE) that was reported to have anti-inflammatory properties. We focused on investigating the levels of activated T lymphocytes and the pro-inflammatory cytokines expressed by macrophages. Methods: Female BALB/c were injected with DMBA subcutaneously. The DMBA exposed mice were given CRE orally in three different doses; 63.33, 158.4, and 316.8 mg/kg. After 14 days, the levels of activated T lymphocytes and pro-inflammatory cytokines were analyzed using flow cytometry. Graphical analysis was done with FlowJo v10 and followed by statistical analysis. Results: The treatment of CRE reduced the population of CD4 and CD8 T cells. The number of activated CD4 and CD8 T cells were also significantly suppressed. The population of macrophages marked by CD11b cells was significantly reduced. Finally, the CRE treatment suppressed the levels of TNF-α, IFN-γ, IL-1β, and IL-6 expressed by macrophages. Conclusion: Our findings suggest that CRE could be a potential agent useful in therapeutic approaches for curing the disease caused by aberrant cells.

scholarly journals Effect of TU‐100 on Peyer's patches in a bacterial translocation rat model

2021 ◽  
Author(s):  
Chie Takasu ◽  
Katsuki Miyazaki ◽  
Kozo Yoshikawa ◽  
Masaaki Nishi ◽  
Takuya Tokunaga ◽  
...  
Keyword(s):  
Bacterial Translocation ◽  
Rat Model ◽  
Peyer's Patches ◽  
Peyer’S Patches

scholarly journals Involvement of calcium-sensing receptor activation in the alleviation of intestinal inflammation in a piglet model by dietary aromatic amino acid supplementation

2018 ◽  
Vol 120 (12) ◽  
pp. 1321-1331 ◽  
Author(s):  
Hongnan Liu ◽  
Bie Tan ◽  
Bo Huang ◽  
Jianjun Li ◽  
Jing Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Inflammatory Cytokines ◽  
Intestinal Inflammation ◽  
Aromatic Amino Acids ◽  
Dietary Supplementation ◽  
Basal Diet ◽  
Signalling Pathway ◽  
Protein Levels ◽  
Pro Inflammatory Cytokines

AbstractCa2+-sensing receptor (CaSR) represents a potential therapeutic target for inflammatory bowel diseases and strongly prefers aromatic amino acid ligands. We investigated the regulatory effects of dietary supplementation with aromatic amino acids – tryptophan, phenylalanine and tyrosine (TPT) – on the CaSR signalling pathway and intestinal inflammatory response. The in vivo study was conducted with weanling piglets using a 2 × 2 factorial arrangement in a randomised complete block design. Piglets were fed a basal diet or a basal diet supplemented with TPT and with or without inflammatory challenge. The in vitro study was performed in porcine intestinal epithelial cell line to investigate the effects of TPT on inflammatory response using NPS-2143 to inhibit CaSR. Dietary supplementation of TPT alleviated histopathological injury and decreased myeloperoxidase activity in intestine challenged with lipopolysaccharide. Dietary supplementation of TPT decreased serum concentration of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-12, granulocyte-macrophage colony-stimulating factor, TNF-α), as well as the mRNA abundances of pro-inflammatory cytokines in intestine but enhanced anti-inflammatory cytokines IL-4 and transforming growth factor-β mRNA levels compared with pigs fed control diet and infected by lipopolysaccharide. Supplementation of TPT increased CaSR and phospholipase Cβ2 protein levels, but decreased inhibitor of NF-κB kinase α/β and inhibitor of NF-κB (IκB) protein levels in the lipopolysaccharide-challenged piglets. When the CaSR signalling pathway was blocked by NPS-2143, supplementation of TPT decreased the CaSR protein level, but enhanced phosphorylated NF-κB and IκB levels in IPEC-J2 cells. To conclude, supplementation of aromatic amino acids alleviated intestinal inflammation as mediated through the CaSR signalling pathway.

Chronic allergy to dietary ovalbumin induces lymphocyte migration to rat small intestinal mucosa that is inhibited by MAdCAM-1

2004 ◽  
Vol 286 (5) ◽  
pp. G702-G710 ◽  
Author(s):  
Toshiko Ogawa ◽  
Soichiro Miura ◽  
Yoshikazu Tsuzuki ◽  
Takashi Ogino ◽  
Ken Teramoto ◽  
...  
Keyword(s):  
Food Allergy ◽  
T Lymphocytes ◽  
Intestinal Mucosa ◽  
Morphological Changes ◽  
Peyer's Patches ◽  
Brown Norway ◽  
Peyer’S Patches ◽  
Small Intestinal Mucosa ◽  
Lymphocyte Migration ◽  
Small Intestinal

Few models have described a chronic food allergy with morphological changes in the intestinal mucosa. Here we established an ovalbumin (OVA)-induced, cell-mediated, allergic rat model and examined lymphocyte migration in the gut. Brown Norway rats were intraperitoneally sensitized to OVA and then given 10 mg OVA/day by gastric intubation for 6 wk. Lymphocyte subsets and adhesion molecules were examined immunohistochemically, and the migration of T lymphocytes to microvessels of Peyer's patches and villus mucosa was observed by using an intravital microscope. Serum OVA-specific IgG and IgE levels were increased in animals repeatedly exposed to OVA. Significant villus atrophy and increased crypt depth was accompanied by increased infiltration of T lymphocytes in the small intestinal mucosa of the group given OVA. Expression of rat mast cell protease II and of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was also increased in these groups. The administration of anti-MAdCAM-1 antibody significantly attenuated the OVA-induced changes in the mucosal architecture and in CD4 T lymphocyte infiltration. Intravital observation demonstrated that in rats with a chronic allergy, T lymphocytes significantly accumulated in villus microvessels as well as in Peyer's patches via a MAdCAM-1-dependent process. Our model of chronic food allergy revealed that lymphocyte migration was increased with MAdCAM-1 upregulation.

scholarly journals The Proinflammatory Response Induced by Wild-Type Yersinia pseudotuberculosis Infection Inhibits Survival of yop Mutants in the Gastrointestinal Tract and Peyer's Patches

2006 ◽  
Vol 74 (3) ◽  
pp. 1516-1527 ◽  
Author(s):  
Lauren K. Logsdon ◽  
Joan Mecsas
Keyword(s):  
Yersinia Pseudotuberculosis ◽  
Intestinal Inflammation ◽  
Peyer's Patches ◽  
Host Responses ◽  
Infection Model ◽  
Peyer’S Patches ◽  
Wild Type ◽  
Single Strain ◽  
Infection Models ◽  
Ifn Γ

ABSTRACT Single-strain infections and coinfections are frequently used to assess roles of virulence factors in infected tissues. After oral inoculation of mice, Yersinia pseudotuberculosis yopE and yopH mutants colonize the intestines and Peyer's patches in single-strain infections but fail to persist in competition with wild-type Y. pseudotuberculosis, indicating that these two infection models provide different insights into the roles of Yops. To determine how wild-type Y. pseudotuberculosis hinders yop mutant survival, yop mutant colonization and host responses were investigated in several different infection models that isolated specific features of wild-type Y. pseudotuberculosis infection. Infection with wild-type Y. pseudotuberculosis caused significantly more inflammation than yop mutants. Results from coinfections of gamma interferon (IFN-γ)−/− mice revealed that IFN-γ-regulated defenses target these mutants, suggesting that YopE and YopH protect Y. pseudotuberculosis from these defenses in BALB/c mice. We developed an oral-intraperitoneal infection model to evaluate the effects of spleen and liver colonization by Y. pseudotuberculosis on yop mutants in the intestines. Spleen and liver infection increased inflammation and decreased yop mutant survival in the intestines, indicating that infection of these organs has consequences in intestinal tissues. Finally, competition infections with Y. pseudotuberculosis mutants with various abilities to induce inflammation demonstrated that survival of the yopE, but not the yopH, mutant was consistently decreased in inflamed tissues. In summary, infection with Y. pseudotuberculosis in intestinal and systemic sites induces intestinal inflammation, which decreases yop mutant survival. Thus, competition studies with wild-type yersiniae reveal critical roles of Yops in combating host responses to a normal virulent infection.

A Phase I/II Study of IPH1101 (BrHPP), Specific Agonist of Vã9Vä2 T Lymphocytes, in Combination with Rituximab Re-Treatment in Patients with Follicular Lymphoma. Interim Phase I Data.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1002-1002
Author(s):  
Guy Laurent ◽  
Jean François Rossi ◽  
Eric W Van Den Neste ◽  
Fabien Audibert ◽  
Hervé Ghesquières ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Phase I ◽  
Follicular Lymphoma ◽  
Dose Level ◽  
Inflammatory Cytokines ◽  
Γδ T Cells ◽  
Low Doses ◽  
Grade 3 ◽  
Pro Inflammatory Cytokines

Abstract Background: Unconventional γδ T lymphocytes are innate immunity effectors bearing very strong anti-tumoral activity. Previous studies have documented that malignant B cells are highly sensitive to γδ T cells mediated cellular toxicity. IPH1101 is a chemically-synthesized, specific antigen for γδ T cells: IPH1101 triggers the synthesis of pro-inflammatory cytokines by γδ T cells - inducing the recruitment of other cell effectors and facilitating implementation of an adaptive response - and potentiates the direct cytotoxic activity of γδ T cells against a large number of tumor B-cell lines. Also, IPH1101-activation of γδ T cells in the presence of low doses of IL-2 leads to their proliferation and differentiation into effectors capable of mediating ADCC. ADCC is the main known molecular mechanism underlying rituximab bioactivity. Increasing the number and the activation of killer lymphocytes mediating ADCC is crucial for therapeutic potency and deserves to be tested in a clinical trial. The purpose of this study is to assess the clinical efficacy, the biological activity, and the safety of the association of IPH1101 with low doses of IL-2, combined to a standard rituximab re-treatment, in patients with Follicular Lymphoma. Method: This is an open label, multinational study consisting of a Phase I like dose-escalation part, followed by Phase II part. Here are reported the Phase I part results. The study population is patients presenting Follicular non-Hodgkin’s Lymphoma, relapsing after 1 or 2 lines of previous therapy, with at least 1 rituximab-containing line. Rituximab (375 mg/m2) was administered 4 times weekly. IPH1101 (750 mg/m2) was administered i.v. three times (every 3 weeks), the first administration being one day after the second rituximab infusion. IL-2 courses consisted in s.c. daily administrations for 5 days, starting on the same day of each IPH1101 administration. All patients participating in this Phase I like period were to be enrolled sequentially with an interval of at least 15 days for evaluation of potential dose limiting toxicity (DLT) occurrence. Results: Six patients were part of the phase I: 3 at IL-2 dose level of 4 MIU and 3 at IL-2 dose level 8 MIU, the targeted dose. No patient presented a DLT as defined in the protocol. One patient treated at the dose level of 8 MIU withdrew the study treatment after the second administration of IL-2 of cycle 2 mainly due to grade 3 asthenia (SAE) and grade 2 vomiting and epigastralgia. At dose level IL-2 of 4 MIU, 2 SAEs were reported: a grade 3 hypotension and a grade 3 ALAT elevation. Most reported adverse events were mild or moderate, mainly nausea, IL-2 injection site reaction, vomiting, diarrhoea, and grade 1 or 2 pyrexia. Their frequency was higher in the cohort treated with 8 MIU of IL2. Pharmacology of IPH1101/IL-2 in this phase I part, based on a weekly monitoring of blood γδ T cells and on dosages of early released plasma cytokines, shows γδ T cells are very efficiently expanded, in an IL-2 dose-dependent fashion and with slow return to baseline. Pro-inflammatory cytokines are released at each IPH1101/IL-2 injections. No unexpected immuno-biological event was reported. Conclusion: These observations showing a good safety and immuno-biological efficacy profile of the combination of rituximab, IPH1101 and low dose IL-2, have allowed the start of the Phase II part of the study with IPH1101/ IL-2 dose of 8 MIU combined with rituximab in patients with follicular lymphoma. The recruitment is ongoing.

KIR Genetics Modifies Susceptibility to Inflammatory Disorder by Reprogramming Human Natural Killer Cell Function

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3282-3282
Author(s):  
Chao Ma ◽  
Lin Lin ◽  
Henry Erlich ◽  
Elizabeth Trachtenberg ◽  
Stephan Targan ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Inflammatory Cytokines ◽  
Cd4 T Cells ◽  
Culture Media ◽  
Killer Cell ◽  
Cellular Mechanism ◽  
Activation Threshold ◽  
Pro Inflammatory Cytokines

Abstract Abstract 3282 Innate lymphocytes can play both protective and pathogenic roles in chronic inflammatory disorders. Recently, killer-cell immunoglobulin-like receptors (KIRs) and its cognitive ligands - human leukocyte antigen (HLA) class I molecules - were identified as genetic risk factors for Crohn's Disease (CD), a common inflammation symptom. Natural killer (NK) cells, the major KIR-expressing cell type, can be educated through KIR-HLA ligation. To uncover the cellular mechanism that determines CD susceptibility, we utilize a novel single-cell functional proteomics microchip and other highly-multiplexed assays (Ma, C. et al. Nature Medicine, 2011, 17, 738–743). We show that, in genetically pertinent individuals, natural killer (NK) cells are functionally reprogrammed to modulate the activation threshold of CD4+ T cells, a major cellular mediator of chronic inflammation. Genetic study of 455 CD patients bearing the AA haplotype identifies that the HLA-C1/C1 allotype, ligand of the KIR2DL3 receptor, is significantly enriched (p<0.0001). Moreover, when evaluating the secretion of 20 cytokines from single purified NK cells that are retrieved from the peripheral blood, we observe that NK cells expressing KIR2DL3 were strongly polarized to robustly produce a myriad of pro-inflammatory cytokines and chemoattractants in copious amounts. Comparing to those from other subjects, NK cells from HLA-C1/C1 subjects produce significantly increased level (p<0.05) of 11 soluble mediators, including TNF, INF-g, ILs, and CCLs. Furthermore, among all NK cells within the HLA-C1/C1 subjects, NK cells expressing KIR2DL3 receptors are the most potent to produce cytokines (2-log higher) and exhibit the highest polyfunctionality. These observations are also confirmed by intracellular staining and ELISA assay of NK cell culture media. Most importantly, the KIR-educated NK cells can strongly augment the activation and proliferation of CD4+ T cells. As shown in autologous NK and CD4+ T cell co-culture assay, CD4+ T cells proliferate aggressively in the presence of NK cells in a dose-dependent fashion (R2=0.99). NK surface costimulatory molecules blockage and NK-CD4+ T cells transwell-separation experiments indicate that this augmentation is not contact-dependent. On the other hand, NK cytokine depletion and ELISA essay of the co-culture media confirmed that soluble factors, such as ILs, IFN-g and TNF, activate CD4+ T cells. KIR2DL3 signaling-mediated education licenses NK cells the capacity to secrete large amounts of pro-inflammatory cytokines and chemokines, which in turn lowers activation threshold of CD4+ T cells and increases susceptibility to chronic inflammation disorders. Our study establishes, for the first time, an immunologic cellular mechanism that explains the KIR genetics-based susceptibility to CD and other chronic inflammatory syndromes. Disclosures: No relevant conflicts of interest to declare.

Subpopulations of T-lymphocytes in Peyer's patches: Sensitivity to antilymphocyte serum and adult thymectomy

1977 ◽  
Vol 33 (4) ◽  
pp. 526-528 ◽  
Author(s):  
D. Vuitton ◽  
R. Eloy ◽  
F. Gosse ◽  
A. Pousse ◽  
J. F. Grenier
Keyword(s):  
T Lymphocytes ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Antilymphocyte Serum
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