Immunological mechanisms involved in probiotic-mediated protection against Citrobacter rodentium-induced colitis

2016 ◽  
Vol 7 (3) ◽  
pp. 397-407 ◽  
Author(s):  
Y. Jiang ◽  
G. Yang ◽  
F. Meng ◽  
W. Yang ◽  
J. Hu ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Lactobacillus Rhamnosus ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Protective Effects ◽  
Citrobacter Rodentium ◽  
Mesenteric Lymph Nodes ◽  
Immunological Mechanisms ◽  
Inflammatory Bowel ◽  
Factor Α

Inflammatory bowel disease is a group of chronic, incurable inflammatory disorders of the gastrointestinal tract that cause severe diarrhoea, intestinal inflammation, pain, fatigue and weight loss. In this study, we first developed a model of Citrobacter rodentium-induced colitis and then evaluated the protective effects of selected probiotics on inflammation. The results showed that administration of a combination of probiotics including Lactobacillus rhamnosus ATCC 53103, Lactobacillus acidophilus ATCC 4356 and Lactobacillus plantarum A significantly increased the production of CD11c+ dendritic cells in the spleen (3.62% vs phosphate buffered saline (PBS)-treated control, P<0.01) and mesenteric lymph nodes (MLNs). In addition, the presence of probiotics significantly up-regulated the development of CD4+/CD25+/Foxp3+ regulatory T cells in MLNs by approximately 2.07% compared to the effect observed in the PBS-treated control (P<0.01) and down-regulated the expression of inflammatory cytokines, including interleukin-17, tumour necrosis factor-α and interferon-γ, by 0.11, 0.11 and 0.15%, respectively, compared to the effect observed in the PBS-treated control (P<0.01).These effects conferred protection against colitis, as shown by histopathological analyses.

scholarly journals Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 539
Author(s):  
Bahez Gareb ◽  
Antonius T. Otten ◽  
Henderik W. Frijlink ◽  
Gerard Dijkstra ◽  
Jos G. W. Kosterink
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Genetically Modified Organisms ◽  
Intestinal Inflammation ◽  
Systemic Exposure ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

scholarly journals Inhibitory Effects of the Two Novel TSPO Ligands 2-Cl-MGV-1 and MGV-1 on LPS-induced Microglial Activation

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 486 ◽  
Author(s):  
Sheelu Monga ◽  
Rafi Nagler ◽  
Rula Amara ◽  
Abraham Weizman ◽  
Moshe Gavish
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Metabolism ◽  
Interferon Γ ◽  
Translocator Protein ◽  
Ros Generation ◽  
Protective Effects ◽  
Neuronal Progenitor ◽  
Cytokines And Chemokines ◽  
Factor Α

The 18 kDa translocator protein (TSPO) ligands 2-Cl-MGV-1 and MGV-1 can attenuate cell death of astrocyte-like cells (U118MG) and induce differentiation of neuronal progenitor cells (PC-12). Lipopolysaccharide (LPS) is a bacterial membrane endotoxin that activates cellular inflammatory pathways by releasing pro-inflammatory molecules, including cytokines and chemokines. The aim of the present study was to assess the immuno-modulatory effect of TSPO ligands in activated microglial cells. We demonstrated that the TSPO ligands 2-Cl-MGV-1 and MGV-1 can prevent LPS-induced activation of microglia (BV-2 cell line). Co-treatment of LPS (100 ng/mL) with these TSPO ligands (final concentration- 25 µM) reduces significantly the LPS-induced release of interleukin-6 (IL-6) from 16.9-fold to 2.5-fold, IL-β from 8.3-fold to 1.6-fold, interferon-γ from 16.0-fold to 2.2-fold, and tumor necrosis factor-α from 16.4-fold to 1.8-fold. This anti-inflammatory activity seems to be achieved by inhibition of NF-κB p65 activation. Assessment of initiation of ROS generation and cell metabolism shows significant protective effects of these two novel TSPO ligands. The IL-10 and IL-13 levels were not affected by any of the TSPO ligands. Thus, it appears that the ligands suppress the LPS-induced activation of some inflammatory responses of microglia. Such immunomodulatory effects may be relevant to the pharmacotherapy of neuro-inflammatory diseases.

scholarly journals Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon

2017 ◽  
Vol 131 (21) ◽  
pp. 2611-2626 ◽  
Author(s):  
Daniel G. Couch ◽  
Chris Tasker ◽  
Elena Theophilidou ◽  
Jonathan N. Lund ◽  
Saoirse E. O’Sullivan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Human Colon ◽  
Interferon Γ ◽  
Cytokine Levels ◽  
Drug Treatments ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Trpv1 Antagonist ◽  
Factor Α

Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Design: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55. Results: IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti-inflammatory in IBD and appendicitis explants. Conclusion: PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy.

The ability of Warburgia salutaris extracts to protect against crystalline silica-induced cell injury

2008 ◽  
Vol 27 (11) ◽  
pp. 827-835 ◽  
Author(s):  
M Leshwedi ◽  
V Steenkamp ◽  
M Dutton ◽  
M Gulumian
Keyword(s):  
Lipid Peroxidation ◽  
Transcription Factor ◽  
Cell Injury ◽  
Antioxidant Properties ◽  
Interferon Γ ◽  
Crystalline Silica ◽  
Protective Effects ◽  
Carcinogenic Effects ◽  
Dna Strand ◽  
Factor Α

In Southern Africa, the medicinal plant Warburgia salutaris is commonly used for the treatment of inflammatory and other diseases. The methanol extracts of W. salutaris were investigated with regard to a) production of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interferon-γ; b) activation of the transcription factor nuclear factor kappa B; and c) induction of deoxyribonucleic acid (DNA) damage and lipid peroxidation in the presence of crystalline silica particles. Due to its antioxidant properties, extracts of W. salutaris showed protective effects against crystalline silica-induced inflammatory cytokine expression, activation of nuclear transcription factor-κB, DNA strand breakage, and lipid peroxidation. Hence, W. salutaris may be a potential therapeutic agent against the fibrogenic and carcinogenic effects of crystalline silica.

NADPH oxidases and cancer

2015 ◽  
Vol 128 (12) ◽  
pp. 863-875 ◽  
Author(s):  
Krishnendu Roy ◽  
Yongzhong Wu ◽  
Jennifer L. Meitzler ◽  
Agnes Juhasz ◽  
Han Liu ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Interferon Γ ◽  
Nadph Oxidases ◽  
Inflammatory Stress ◽  
Over Expression ◽  
Wide Range ◽  
Membrane Bound ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Respiratory Burst Oxidase

The mechanism by which reactive oxygen species (ROS) are produced by tumour cells remained incompletely understood until the discovery over the last 15 years of the family of NADPH oxidases (NOXs 1–5 and dual oxidases DUOX1/2) which are structural homologues of gp91phox, the major membrane-bound component of the respiratory burst oxidase of leucocytes. Knowledge of the roles of the NOX isoforms in cancer is rapidly expanding. Recent evidence suggests that both NOX1 and DUOX2 species produce ROS in the gastrointestinal tract as a result of chronic inflammatory stress; cytokine induction (by interferon-γ, tumour necrosis factor α, and interleukins IL-4 and IL-13) of NOX1 and DUOX2 may contribute to the development of colorectal and pancreatic carcinomas in patients with inflammatory bowel disease and chronic pancreatitis, respectively. NOX4 expression is increased in pre-malignant fibrotic states which may lead to carcinomas of the lung and liver. NOX5 is highly expressed in malignant melanomas, prostate cancer and Barrett's oesophagus-associated adenocarcinomas, and in the last it is related to chronic gastro-oesophageal reflux and inflammation. Over-expression of functional NOX proteins in many tissues helps to explain tissue injury and DNA damage from ROS that accompany pre-malignant conditions, as well as elucidating the potential mechanisms of NOX-related damage that contribute to both the initiation and the progression of a wide range of solid and haematopoietic malignancies.

scholarly journals TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis

2010 ◽  
Vol 207 (5) ◽  
pp. 1057-1066 ◽  
Author(s):  
Mario Noti ◽  
Nadia Corazza ◽  
Christoph Mueller ◽  
Barbara Berger ◽  
Thomas Brunner
Keyword(s):  
Inflammatory Bowel Disease ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Therapeutic Administration ◽  
Necrosis Factor

Although tumor necrosis factor (α) (TNF) exerts proinflammatory activities in a variety of diseases, including inflammatory bowel disease, there is increasing evidence for antiinflammatory actions of TNF. In contrast, glucocorticoids (GCs) are steroid hormones that suppress inflammation, at least in part by regulating the expression and action of TNF. We report that TNF induces extraadrenal production of immunoregulatory GCs in the intestinal mucosa during acute intestinal inflammation. The absence of TNF results in a lack of colonic GC synthesis and exacerbation of dextran sodium sulfate–induced colitis. TNF seems to promote local steroidogenesis by directly inducing steroidogenic enzymes in intestinal epithelial cells. Therapeutic administration of TNF induces GC synthesis in oxazolone-induced colitis and ameliorates intestinal inflammation, whereas inhibition of intestinal GC synthesis abrogates the therapeutic effect of TNF. These data show that TNF suppresses the pathogenesis of acute intestinal inflammation by promoting local steroidogenesis.

scholarly journals Protective and Anti-Inflammatory Effects of Protegrin-1 on Citrobacter rodentium Intestinal Infection in Mice

2021 ◽  
Vol 22 (17) ◽  
pp. 9494
Author(s):  
Celina Osakowicz ◽  
Lauren Fletcher ◽  
Jeff L. Caswell ◽  
Julang Li
Keyword(s):  
Antimicrobial Activity ◽  
Broad Spectrum ◽  
Intestinal Inflammation ◽  
Clinical Signs ◽  
Significant Rise ◽  
Resistant Bacteria ◽  
Protective Effects ◽  
Citrobacter Rodentium ◽  
Intestinal Infection ◽  
Infectious Colitis

Infectious intestinal colitis, manifesting as intestinal inflammation, diarrhea, and epithelial barrier disruption, affects millions of humans worldwide and, without effective treatment, can result in death. In addition to this, the significant rise in antibiotic-resistant bacteria poses an urgent need for alternative anti-infection therapies for the treatment of intestinal disorders. Antimicrobial peptides (AMPs) are potential therapies that have broad-spectrum antimicrobial activity due to their (1) unique mode of action, (2) broad-spectrum antimicrobial activity, and (3) protective role in GI tract maintenance. Protegrin-1 (PG-1) is an AMP of pig origin that was previously shown to reduce the pathological effects of chemically induced digestive tract inflammation (colitis) and to modulate immune responses and tissue repair. This study aimed to extend these findings by investigating the protective effects of PG-1 on pathogen-induced colitis in an infection study over a 10-day experimental period. The oral administration of PG-1 reduced Citrobacter rodentium intestinal infection in mice as evidenced by reduced histopathologic change in the colon, prevention of body weight loss, milder clinical signs of disease, and more effective clearance of bacterial infection relative to challenged phosphate-buffered saline (PBS)-treated mice. Additionally, PG-1 treatment altered the expression of various inflammatory mediators during infection, which may act to resolve inflammation and re-establish intestinal homeostasis. PG-1 administered in its mature form was more effective relative to the pro-form (ProPG-1). To our knowledge, this is the first study demonstrating the protective effects of PG-1 on infectious colitis.

S1731 Differential Regulation of Interleukin-17 and Interferon-γ Production in Inflammatory Bowel Disease

2009 ◽  
Vol 136 (5) ◽  
pp. A-258
Author(s):  
Laura Rovedatti ◽  
Takahiro Kudo ◽  
Paolo Biancheri ◽  
David S. Rampton ◽  
Neel Sengupta ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Interferon Γ ◽  
Differential Regulation ◽  
Interleukin 17 ◽  
Inflammatory Bowel
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