Escherichia coli Nissle 1917 Distinctively Modulates T-Cell Cycling and Expansion via Toll-Like Receptor 2 Signaling

ABSTRACT Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be efficacious for the treatment of inflammatory bowel diseases, the underlying mechanisms of action still remain elusive. The aim of the present study was to analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3-stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA content, and caspase 3 expression were measured by flow cytometry to assess cell cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis modulators were determined by immunoblotting, and cytokine profiles were determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E. coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling. E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein expression, contributing to the reduction of T-cell proliferation. E. coli Nissle 1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor necrosis factor α, and gamma interferon but increased IL-10 production in PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2 dependent. The differential reaction of circulating and tissue-bound T cells towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle 1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the expansion of newly recruited T cells into the mucosa and limit intestinal inflammation, while already activated tissue-bound T cells may eliminate deleterious antigens in order to maintain immunological homeostasis.

Download Full-text

To Ki or Not to Ki: Re-Evaluating the Use and Potentials of Ki-67 for T Cell Analysis

Frontiers in Immunology ◽

10.3389/fimmu.2021.653974 ◽

2021 ◽

Vol 12 ◽

Author(s):

Francesca Di Rosa ◽

Andrea Cossarizza ◽

Adrian C. Hayday

Keyword(s):

Cell Cycle ◽

T Cells ◽

T Cell ◽

Peripheral Blood ◽

Human Peripheral Blood ◽

Human Lymphocytes ◽

Lymphoid Tissues ◽

Ki 67 ◽

Organ Specific ◽

Dual Staining

This study discusses substantive advances in T cell proliferation analysis, with the aim to provoke a re-evaluation of the generally-held view that Ki-67 is a reliable proliferation marker per se, and to offer a more sensitive and effective method for T cell cycle analysis, with informative examples in mouse and human settings. We summarize recent experimental work from our labs showing that, by Ki-67/DNA dual staining and refined flow cytometric methods, we were able to identify T cells in the S-G2/M phases of the cell-cycle in the peripheral blood (collectively termed “T Double S” for T cells in S-phase in Sanguine: in short “TDS” cells). Without our refinement, such cells may be excluded from conventional lymphocyte analyses. Specifically, we analyzed clonal expansion of antigen-specific CD8 T cells in vaccinated mice, and demonstrated the potential of TDS cells to reflect immune dynamics in human blood samples from healthy donors, and patients with type 1 diabetes, infectious mononucleosis, and COVID-19. The Ki-67/DNA dual staining, or TDS assay, provides a reliable approach by which human peripheral blood can be used to reflect the dynamics of human lymphocytes, rather than providing mere steady-state phenotypic snapshots. The method does not require highly sophisticated “-omics” capabilities, so it should be widely-applicable to health care in diverse settings. Furthermore, our results argue that the TDS assay can provide a window on immune dynamics in extra-lymphoid tissues, a long-sought potential of peripheral blood monitoring, for example in relation to organ-specific autoimmune diseases and infections, and cancer immunotherapy.

Download Full-text

Ex Vivo Modulation of Donor Cells Results in Enhanced Survival and Reduced Gvhd Mortality

Blood ◽

10.1182/blood.v126.23.1884.1884 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1884-1884 ◽

Cited By ~ 2

Author(s):

Lisa Guerrettaz ◽

Newsha Sahaf ◽

Leah Mitchell ◽

Chris Lynn ◽

Sarah Raynel ◽

...

Keyword(s):

Cell Cycle ◽

T Cells ◽

T Cell ◽

Immune Tolerance ◽

Peripheral Blood ◽

Ex Vivo ◽

T Cell Responses ◽

Cell Transplant ◽

Cell Responses ◽

Mobilized Peripheral Blood

Abstract Allogeneic hematopoietic stem cell transplant (HSCT) represents a potential curative treatment for a number of life-threatening blood malignancies. The utility of this treatment regimen, however, is limited by a number of serious complications including graft versus host disease, which occurs in approximately half of all transplant patients. Standard-of-care for treating acute GvHD has remained unchanged for several decades and consists of high doses of steroids, which are only effective in approximately 35 percent of the cases. Therefore, the reduction of GvHD represents a large unmet medical need, and new approaches are needed to effectively attenuate GvHD. Here we present a fundamentally novel strategy for potentially reducing GVHD - by modulating donor mobilized peripheral blood cells with small molecules prior to HSCT, a programmed mobilized peripheral blood (mPB) allogeneic graft, with reduced T-cell alloreactivity, can be administered as the hematopoietic cell source for HSCT. To this end, we applied our screening platform to identify a combination of small molecule modulators (FT1050, FT4145) that promote the activation of genes implicated in cell cycle, immune tolerance and anti-viral properties of T cells, as well as in the survival, proliferation and engraftment potential of CD34+ cells. Genome-wide expression analysis of the T-cell compartment of mobilized peripheral blood following treatment with FT1050+FT4145 revealed the induction of genes involved in cell cycle (e.g., CCND1, CCNE1), immune tolerance (e.g., ALDH, AREG) and anti-viral properties (e.g., EFNB2). To further assess the therapeutic impact of ex vivo programming with FT1050 and FT4145, a number of T cell assays to assess T cell phenotype and function were conducted on mPB. Overall, ex vivo programming of mPB resulted in reduced allogeneic T cell responses and was accompanied by reduced capacity of modulated T cells to produce Interferon Gamma (IFN-ɣ). Concomitantly, the ability of the modulated T cells to make Interleukin 4 (IL-4) and 10 (IL-10) was enhanced, suggesting a polarization of these cells towards a less inflammatory functional state. This was further evidenced by increased surface expression of an immune-inhibitory molecule, PD1, and reduced expression of the activation markers 41BB and ICOS. We next examined the potential beneficial role of ex vivo programming with FT1050+FT4145 in a major histocompatibility complex (MHC) mis-matched HSCT mouse model. Briefly, lethally irradiated BALB/c mice received bone marrow and splenocytes from C57BL/6 donor mice pulse treated with vehicle or FT1050+FT4145. Significantly less GvHD, as determined by survival, weight loss, GVHD score (diarrhea, inactivity, hunched posture, ruffled fur, eye lesion, snout swelling/skin integrity), cytokine production and histopathology of GvHD target organs was observed in recipients receiving FT1050+FT4145 treated cells as compared to those receiving vehicle treated cells. In addition, we observed increased levels of donor T regulatory cells (Tregs) in secondary lymphoid organs concomitant with decreased levels of circulating IFN-ɣ in recipients receiving FT1050+FT4145 treated cells. Based on the attenuation of alloreactive T-cell responses in these preclinical studies, we believe our findings provide a compelling scientific basis to support the clinical evaluation of ex vivo programmed mobilized peripheral blood in patients undergoing HSCT for the treatment of hematologic malignancies. Disclosures Levin: Fate Therapeutics, Inc: Employment, Equity Ownership. Shoemaker:Fate Therapeutics Inc: Employment.

Download Full-text

Escherichia coli Strain Nissle 1917 Ameliorates Experimental Colitis via Toll-Like Receptor 2- and Toll-Like Receptor 4-Dependent Pathways

Infection and Immunity ◽

10.1128/iai.01449-05 ◽

2006 ◽

Vol 74 (7) ◽

pp. 4075-4082 ◽

Cited By ~ 120

Author(s):

A. Grabig ◽

D. Paclik ◽

C. Guzy ◽

A. Dankof ◽

D. C. Baumgart ◽

...

Keyword(s):

Escherichia Coli ◽

T Cells ◽

Knockout Mice ◽

Selective Reduction ◽

Experimental Colitis ◽

Defense Responses ◽

Coli Strain ◽

Cytokine Secretion ◽

Toll Like Receptor ◽

E Coli

ABSTRACT Toll-like receptors (TLRs) are key components of the innate immune system that trigger antimicrobial host defense responses. The aim of the present study was to analyze the effects of probiotic Escherichia coli Nissle strain 1917 in experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via administration of 5% dextran sodium sulfate (DSS). Mice were treated with either 0.9% NaCl or 107 E. coli Nissle 1917 twice daily, followed by the determination of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2 knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4 knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction of gamma interferon secretion was observed after E. coli Nissle 1917 treatment. In TLR-4 knockout mice, cytokine secretion was almost undetectable and not modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and human T cells increased TLR-2 and TLR-4 protein expression in T cells and increased NF-κB activity via TLR-2 and TLR-4. In conclusion, our data provide evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in mice via TLR-2- and TLR-4-dependent pathways.

Download Full-text

Inhibition of Antigen-Specific and Nonspecific Stimulation of Bovine T and B Cells by Lymphostatin from Attaching and Effacing Escherichia coli

Infection and Immunity ◽

10.1128/iai.00845-16 ◽

2016 ◽

Vol 85 (2) ◽

Cited By ~ 2

Author(s):

Robin L. Cassady-Cain ◽

Elizabeth A. Blackburn ◽

Charlotte R. Bell ◽

Elizaveta Elshina ◽

Jayne C. Hope ◽

...

Keyword(s):

Escherichia Coli ◽

T Cells ◽

T Cell ◽

B Cells ◽

T Cell Activation ◽

Cell Activation ◽

Interleukin 2 ◽

Content Type ◽

E Coli ◽

Stimulation Of

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are enteric bacterial pathogens of worldwide importance. Most EPEC and non-O157 EHEC strains express lymphostatin (also known as LifA), a chromosomally encoded 365-kDa protein. We previously demonstrated that lymphostatin is a putative glycosyltransferase that is important in intestinal colonization of cattle by EHEC serogroup O5, O111, and O26 strains. However, the nature and consequences of the interaction between lymphostatin and immune cells from the bovine host are ill defined. Using purified recombinant protein, we demonstrated that lymphostatin inhibits mitogen-activated proliferation of bovine T cells and, to a lesser extent, proliferation of cytokine-stimulated B cells, but not NK cells. It broadly affected the T cell compartment, inhibiting all cell subsets (CD4, CD8, WC-1, and γδ T cell receptor [γδ-TCR]) and cytokines examined (interleukin 2 [IL-2], IL-4, IL-10, IL-17A, and gamma interferon [IFN-γ]) and rendered T cells refractory to mitogen for a least 18 h after transient exposure. Lymphostatin was also able to inhibit proliferation of T cells stimulated by IL-2 and by antigen presentation using a Theileria-transformed cell line and autologous T cells from Theileria-infected cattle. We conclude that lymphostatin is likely to act early in T cell activation, as stimulation of T cells with concanavalin A, but not phorbol 12-myristate 13-acetate combined with ionomycin, was inhibited. Finally, a homologue of lymphostatin from E. coli O157:H7 (ToxB; L7095) was also found to possess comparable inhibitory activity against T cells, indicating a potentially conserved strategy for interference in adaptive responses by attaching and effacing E. coli.

Download Full-text

Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

10.21203/rs.2.18314/v2 ◽

2020 ◽

Author(s):

Hanna Helgeland ◽

Ingvild Gabrielsen ◽

Helle Akselsen ◽

Arvind Y.M. Sundaram ◽

Siri Tennebø Flåm ◽

...

Keyword(s):

Cell Cycle ◽

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Peripheral Blood ◽

Cell Subset ◽

Functional Enrichment ◽

Valuable Insight ◽

Thymic Tissue ◽

Adult Peripheral Blood

Abstract Background: The thymus is a highly specialized organ of the immune system where T cell precursors develop and differentiate into self-tolerant CD4+ or CD8+ T cells. No studies to date have investigated how the human transcriptome profiles differ, between T cells still residing in the thymus and T cells in the periphery. Results: We have performed high-throughput RNA sequencing to characterize the transcriptomes of primary single positive (SP) CD4+ and CD8+ T cells from infant thymic tissue, as well as primary CD4+ and CD8+ T cells from infant and adult peripheral blood, to enable the comparisons across tissues and ages. In addition, we have assessed the expression of candidate genes related to autoimmune diseases in thymic CD4+ and CD8+ T cells. The thymic T cells showed the largest number of uniquely expressed genes, suggesting a more diverse transcription in thymic T cells. Comparing T cells of thymic and blood origin, revealed more differentially expressed genes, than between infant and adult blood. Functional enrichment analysis revealed an over-representation of genes involved in cell cycle and replication in thymic T cells, whereas infant blood T cells were dominated by immune related terms. Comparing adult and infant blood T cells, the former was enriched for inflammatory response, cytokine production and biological adhesion, while upregulated genes in infant blood T cells were associated with cell cycle, cell death and gene expression. Conclusion: This study provides valuable insight into the transcriptomes of the human primary SP T cells still residing within the thymus, and offers a unique comparison to primary blood derived T cells. Interestingly, the majority of autoimmune disease associated genes were expressed in one or more T cell subset, however ~11% of these were not expressed in frequently studied adult peripheral blood.

Download Full-text

SslE (YghJ), a Cell-Associated and Secreted Lipoprotein of Neonatal Septicemic Escherichia coli, Induces Toll-Like Receptor 2-Dependent Macrophage Activation and Proinflammation through NF-κB and MAP Kinase Signaling

Infection and Immunity ◽

10.1128/iai.00399-18 ◽

2018 ◽

Vol 86 (9) ◽

Cited By ~ 3

Author(s):

Rima Tapader ◽

Dipro Bose ◽

Pujarini Dutta ◽

Santasabuj Das ◽

Amit Pal

Keyword(s):

Escherichia Coli ◽

Immune Response ◽

Map Kinase ◽

Macrophage Activation ◽

Toll Like Receptor ◽

Content Type ◽

E Coli ◽

Murine Macrophages ◽

A Cell ◽

Toll Like Receptor 2

ABSTRACT SslE (YghJ), a cell surface-associated and secreted lipoprotein, was identified as a potential vaccine candidate for extraintestinal pathogenic Escherichia coli, providing nearly complete protection from sepsis in a mouse model. We earlier found that SslE from neonatal septicemic E. coli could trigger the secretion of various proinflammatory cytokines in murine macrophages, the signaling pathway of which is still obscure. In this study, we showed that SslE specifically binds to Toll-like receptor 2 (TLR2)/TLR1 heterodimers and recruits downstream adaptors MyD88, TIRAP, and TRAF6. In addition, SslE stimulates nuclear translocation of NF-κB and activates different mitogen-activated protein (MAP) kinase signaling cascades specific to the secretion of each cytokine in murine macrophages, which becomes impaired in TLR2 small interfering RNA (siRNA)-transfected cells and in cells blocked with a monoclonal antibody (MAb) against TLR2, suggesting the involvement of TLR2 in NF-κB and MAP kinase activation and subsequent cytokine secretion. Furthermore, our study is the first to show that SslE can stimulate TLR2-dependent production of other proinflammatory hallmarks, such as reactive nitrogen and oxygen species as well as type 1 chemokines, which contribute to the anti-infection immune response of the host. Also, the overexpression of major histocompatibility complex class II (MHC II) and other costimulatory molecules (CD80 and CD86) in macrophages essentially indicates that SslE promotes macrophage activation and M1 polarization, which are crucial in framing the host's innate immune response to this protein, and hence, SslE could be a potent immunotherapeutic target against E. coli sepsis.

Download Full-text

P043 Small intestinal inflammation but not colitis drives pro-inflammatory nutritional antigen-specific T-cell response

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.172 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S154-S155

Author(s):

Y Rodríguez Sillke ◽

M Schumann ◽

D Lissner ◽

F Branchi ◽

R Glauben ◽

...

Keyword(s):

T Cells ◽

Celiac Disease ◽

T Cell ◽

Peripheral Blood ◽

Cell Response ◽

Intestinal Inflammation ◽

T Cell Response ◽

Tnf Α ◽

Food Antigens ◽

Small Intestinal

Abstract Background Inflammatory bowel disease (IBD) represents a dysregulation of the mucosal immune system. The pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC) is linked to the loss of intestinal tolerance and barrier function. The healthy mucosal immune system has previously been shown to be inert against food antigens. Since the small intestine is the main contact surface for antigens and therefore the immunological response, the present study served to analyse food-antigen-specific T cells in the peripheral blood of IBD patients. Methods Peripheral blood mononuclear cells of CD, with an affected small intestine, and UC (colitis) patients, either active or in remission, were stimulated with the following food antigens: gluten, soybean, peanut and ovalbumin. Healthy controls and celiac disease patients were included as controls. Antigen-activated CD4+ T cells in the peripheral blood were analysed by a magnetic enrichment of CD154+ effector T cells and a cytometric antigen-reactive T-cell analysis (‘ARTE’ technology) followed by characterisation of the effector response. Results The effector T-cell response of antigen-specific T cells were compared between CD with small intestinal inflammation and UC where inflammation was restricted to the colon. Among all tested food antigens, the highest frequency of antigen-specific T cells (CD4+CD154+) was found for gluten. Celiac disease patients were included as control, since gluten has been identified as the disease-causing antigen. The highest frequency of gluten antigen-specific T cells was revealed in active CD when compared with UC, celiac disease on a gluten-free diet (GFD) and healthy controls. Ovalbumin-specific T cells were almost undetectable, whereas the reaction to soybean and peanut was slightly higher. But again, the strongest reaction was observed in CD with small intestinal involvement compared with UC. Remarkably, in celiac disease on a GFD only antigen-specific cells for gluten were detected. These gluten-specific T cells were characterised by up-regulation of the pro-inflammatory cytokines IFN-γ, IL-17A and TNF-α. IFN-g was exclusively elevated in CD patients with active disease. Gluten-specific T-cells expressing IL-17A were increased in all IBD patients. Furthermore, T cells of CD patients, independent of disease activity, revealed a high expression of the pro-inflammatory cytokine TNF-α. Conclusion The ‘ARTE’-technique allows to analyse and quantify food antigen specific T cells in the peripheral blood of IBD patients indicating a potential therapeutic insight. These data provide evidence that small intestinal inflammation in CD is key for the development of a systemic pro-inflammatory effector T-cell response driven by food antigens.

Download Full-text

Toll-Like Receptor 2 and 4 Are Expressed on Transplanted T-Cell Subsets and Influence Outcome after Allogeneic Unrelated Peripheral Blood Stem Cell Transplantation.

Blood ◽

10.1182/blood.v110.11.1066.1066 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1066-1066

Author(s):

Uwe Platzbecker ◽

Jan Stoehlmacher ◽

Eray Goekkurt ◽

Caroline Pabst ◽

Christian Thiede ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cd8 T Cells ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Toll Like Receptor ◽

Clinical Endpoints ◽

Blood Stem Cell Transplantation

Abstract Introduction: Recently, Toll-like receptor (TLR) 2 and 4 have been identified as the most important receptors for LPS, which is contained in the cell wall of gram-negative bacteria and is known to be a main inducer of graft versus host disease (GVHD). The role of TLR expressing T-cells within the graft for the induction of GVHD in patients after unrelated peripheral blood stem cell transplantation (PBSCT) is unknown. Methods and patients: We therefore determined by flow cytometry expression of TLR 2 and 4 on T-cells within the graft of 63 patients receiving unrelated PBSCT after intensive conditioning followed by cyclosporine A and methotrexate as GVHD prophylaxis. Additionally, donor specific single nucleotide polymorphisms (SNP) for TLR2 (R753Q), TLR4 (D299G) and TLR4 (Y135A) were determined. The data were finally correlated with clinical endpoints. Results: As expected, TLRs were not expressed on T-cells in peripheral blood of healthy donors (TLR 2: <1.0%, TLR4 <0.5% of T-cells, n=6). In contrast we detected a distinct up-regulation of these receptors on T-cells within the grafts. TLR2 and TLR4 expression on CD4+ T-cells ranged from 1.2%–12.3% (median 3.1%) for TLR2 and from 1.2%–12.0% (median 3.7%) for TLR4. Among the CD8+ T-cells 0.9%–16.1% (median 3.3%) expressed TLR2 and 0.7%–13.3% (median 3.5%) expressed TLR4. The SNP for TLR2 (R753Q) and TLR4 (D299G) was found in 8.6% and 10.3% of the allogeneic donors, respectively but did neither correlate with the expression levels of TLR on T-cells nor with clinical endpoints. Treatment-related mortality from infections was observed in 10 patients (16%). Interestingly, higher expression of TLR2 and 4 on CD4+ but not CD8+ T-cells was significantly associated with an increased cumulative incidence of fatal infections (38% vs. 8% p=0.03 for TLR2 and 37% vs. 9% p=0.007 for TLR4). Neither the overall CD3+, CD4+ and CD8+ cell dose nor the expression of TLR2 and 4 on CD4+ and CD8+ T-cells showed a significant association with the incidence of acute or chronic GVHD or relapse. Conclusion: These data suggest a previously unrecognised up-regulation of TLR, on CD4+ and CD8+ T-cells contained in G-CSF mobilized apheresis products. Whether these phenotypic changes impact on T cell function or patient outcome warrants further investigation.

Download Full-text

The lipopolysaccharide from Escherichia coli O127:B8 induces inflammation and motility disturbances in rabbit ileum

World Rabbit Science ◽

10.4995/wrs.2017.5160 ◽

2017 ◽

Vol 25 (2) ◽

pp. 185

Author(s):

Laura Grasa ◽

Sergio Gonzalo ◽

Alba De Martino ◽

María Divina Murillo

Keyword(s):

Escherichia Coli ◽

Mrna Expression ◽

Intestinal Inflammation ◽

Organ Bath ◽

Toll Like Receptor ◽

Rabbit Ileum ◽

Toll Like Receptor 4 ◽

E Coli ◽

Mucosal Layer ◽

Spontaneous Contractions

The aim of this work was to evaluate the effects of lipopolysaccharide (LPS) from Escherichia coli O127:B8 on the expression of toll-like receptor 4 (TLR4), the histology, and motor function in rabbit ileum. Rabbits were injected intravenously with saline or LPS (100 μg/kg, 2 h). The mRNA expression and localization of TLR4 were determined by reverse transcriptase-PCR and immunofluorescence, respectively. Histological damage induced by LPS was evaluated in sections of ileum stained with haematoxylin and eosin. Contractility studies of ileum were performed in an organ bath. The mRNA expression of TLR4 decreased in the muscular but not in the mucosal layer of rabbits treated with LPS. TLR4 was localised in both the mucosal and muscular layers of rabbit ileum. LPS induced intestinal inflammation and altered the spontaneous contractions and the serotonin-, acetylcholine- and KCl-induced contractions. In conclusion, LPS from E. coli O127:B8 induced a decrease in the mRNA expression of TLR4, an inflammatory response, and changes in the contractility of rabbit ileum.

Download Full-text