Lactobacillus caseiprevents the upregulation of ICAM-1 expression and leukocyte recruitment in experimental colitis

2006 ◽  
Vol 291 (6) ◽  
pp. G1155-G1162 ◽  
Author(s):  
Sandra Angulo ◽  
Marta Llopis ◽  
María Antolín ◽  
Meritxell Gironella ◽  
Miquel Sans ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Lactobacillus Casei ◽  
Experimental Colitis ◽  
Leukocyte Recruitment ◽  
Rat Colon ◽  
Normal Flora ◽  
Trinitrobenzenesulfonic Acid ◽  
Antibody Technique ◽  
Colonic Segment ◽  
Adherent Leukocytes

Lactobacillus casei has been shown to attenuate the severity of experimental colitis. The objective of the present study was to determine whether the effects of L. casei on colitis are related to modulation of leukocyte recruitment into the inflamed intestine. Rats with a colonic segment excluded from fecal transit were surgically prepared. The segment was decontaminated with antibiotics and recolonized with normal flora isolated from the inflamed rat colon, associated or not to L. casei. Control and colitic [2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced] animals were studied. Leukocyte-endothelial cell interactions were characterized in the colonic microcirculation by intravital microscopy, and ICAM-1 and VCAM-1 expression was measured by the radiolabeled antibody technique. Compared with the noninflamed colonic segment, induction of colitis by TNBS provoked a marked increase in the number of leukocytes firmly adherent to the venular wall (0.5 ± 0.1 vs. 2.1 ± 0.6 leukocytes/100 μm, P < 0.01). Colonization with L. casei significantly reduced the number of adherent leukocytes (1.3 ± 0.4 leukocytes/100 μm; P < 0.05) but did not affect the increased rolling interactions associated with the induction of colitis. Compared with the noncolitic group, induction of colitis was associated with a marked increase in ICAM-1 expression (117 ± 4 vs. 180 ± 3 ng antibody/g tissue) that was abrogated when the colitic segment was colonized by L. casei (117 ± 3 ng antibody/g tissue, P < 0.05). However, L. casei administration did not modify VCAM-1 upregulation in colitic animals. L. casei attenuates leukocyte recruitment observed in experimental colitis induced by TNBS. This effect is possibly related to abrogation of ICAM-1 upregulation.

Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis

2006 ◽  
Vol 290 (6) ◽  
pp. G1131-G1137 ◽  
Author(s):  
C. Anthoni ◽  
M. G. Laukoetter ◽  
E. Rijcken ◽  
T. Vowinkel ◽  
R. Mennigen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Endothelial Cell ◽  
Disease Activity ◽  
Experimental Colitis ◽  
Inflammatory Cells ◽  
Boswellic Acid ◽  
Boswellia Serrata ◽  
Antibody Technique ◽  
Dss Colitis ◽  
Anti Inflammatory

Recent clinical trials of the gum resin of Boswellia serrata have shown promising results in patients with ulcerative colitis. The objective of this study was to determine whether a semisynthetic form of acetyl-11-keto-β-boswellic acid (sAKBA), the most potent anti-inflammatory component of the resin, also confers protection in experimental murine colitis induced by dextran sodium sulfate (DSS) to compare its effects with those standard medications of ulcerative colitis like steroids and to examine whether leukocyte-endothelial cell adhesion is a major target of action of sAKBA. Clinical measurements of disease activity and histology were used to assess disease progression, and intravital microscopy was employed to monitor the adhesion of leukocytes and platelets in postcapillary venules of the inflamed colon. sAKBA treatment significantly blunted disease activity as assessed both grossly and by histology. Similarly, the recruitment of adherent leukocytes and platelets into inflamed colonic venules was profoundly reduced in mice treated with sAKBA. Because previous studies in the DSS model have shown that P-selectin mediates these blood cell-endothelial cell interactions, the expression of P-selectin in the colonic microcirculation was monitored using the dual-radiolabeled antibody technique. The treatment of established colitis with sAKBA largely prevented the P-selectin upregulation normally associated with DSS colitis. All of the protective responses observed with sAKBA were comparable to that realized in mice treated with a corticosteroid. Our findings demonstrated an anti-inflammatory effect of sAKBA and indicated that P-selectin-mediated recruitment of inflammatory cells is a major site of action for this novel anti-inflammatory agent.

scholarly journals Mechanisms of platelet and leukocyte recruitment in experimental colitis

2007 ◽  
Vol 293 (5) ◽  
pp. G1054-G1060 ◽  
Author(s):  
Thorsten Vowinkel ◽  
Katherine C. Wood ◽  
Karen Y. Stokes ◽  
Janice Russell ◽  
Anitaben Tailor ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Sodium Sulfate ◽  
Platelet Adhesion ◽  
Tissue Injury ◽  
Leukocyte Adhesion ◽  
Microvascular Dysfunction ◽  
Experimental Colitis ◽  
Dss Colitis ◽  
Adherent Leukocytes

Both leukocytes and platelets accumulate in the colonic microvasculature during experimental colitis, leading to microvascular dysfunction and tissue injury. The objective of this study was to determine whether the recruitment of leukocytes and platelets in inflamed colonic venules are codependent processes. The rolling and adherence of leukocytes and platelets in colonic venules of mice with dextran sodium sulfate (DSS)-induced colitis were monitored by intravital videomicroscopy. DSS elicited an increased recruitment of both rolling and adherent leukocytes and platelets. DSS-colitic mice rendered thrombocytopenic with anti-platelet serum exhibited profound reductions in leukocyte adhesion. Neutropenia, induced with anti-neutrophil serum, significantly reduced the adhesion of leukocytes and the accumulation of platelet-leukocyte aggregates while greatly enhancing the number of platelets that roll and adhere directly to venular endothelial cells. The enhanced platelet adhesion associated with neutropenia was mediated by platelet P-selectin interactions with endothelial cell P-selectin glycoprotein ligand (PSGL-1). DSS colitis was also associated with an increased expression of PSGL-1 in the colonic vasculature. These findings indicate that the recruitment of leukocytes and platelets in inflamed colonic venules are codependent processes.

scholarly journals Leukocyte adhesion is governed by endolysosomal two pore channel 2 (TPC2)

2021 ◽  
Author(s):  
Jonas Goretzko ◽  
Nicole Heitzig ◽  
Katharina Thomas ◽  
Einar Kleinhans Krogsaeter ◽  
Johannes Nass ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Surface ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Pore Channel ◽  
Initial Contact ◽  
Surface Receptors ◽  
Endothelial Cell Surface ◽  
Late Endosomes ◽  
Endothelial Functions

In response to pro-inflammatory challenges including pathogenic attack and tissue damage, the endothelial cell surface is rearranged to present leukocyte-engaging cell surface receptors. The initial contact needed for leukocyte tethering and rolling is mediated via adhesion demand-driven exocytosis of Weibel-Palade bodies (WPB) that contain the leukocyte receptor P-selectin together with the stabilizing co-factor CD63. We found that diminished expression of the endolysosomal non-selective cation channel TPC2 or inhibition of TPC2-mediated Ca2+-release via trans-Ned 19 led to reduced endolysosomal Ca2+ efflux, and blocked transfer of CD63 from late endosomes/lysosomes (LEL) to WPB, and a concomitant loss of P-selectin on the endothelial cell surface. Accordingly, P-selectin-mediated leukocyte recruitment to trans-Ned 19-treated HUVEC under flow was significantly reduced without disturbing VWF exocytosis. Our findings establish the endolysosome-related TPC2 Ca2+ channel as a key element in the maintenance of proper endothelial functions and a potential pharmacological target in the control of inflammatory leukocyte recruitment.

scholarly journals High-fat diet promotes experimental colitis by inducing oxidative stress in the colon

2019 ◽  
Vol 317 (4) ◽  
pp. G453-G462 ◽  
Author(s):  
Xue Li ◽  
Xinzhi Wei ◽  
Yue Sun ◽  
Jie Du ◽  
Xin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Experimental Colitis ◽  
Mucosal Barrier ◽  
Mucosal Inflammation ◽  
High Fat ◽  
Trinitrobenzenesulfonic Acid ◽  
Barrier Permeability ◽  
Inflammatory Bowel ◽  
Colitis Model

Diets high in animal fats are associated with increased risks of inflammatory bowel disease, but the mechanism remains unclear. In this study, we investigated the effect of high-fat diet (HFD) on the development of experimental colitis in mice. Relative to mice fed low-fat diet (LFD), HFD feeding for 4 wk increased the levels of triglyceride, cholesterol, and free fatty acids in the plasma as well as within the colonic mucosa. In an experimental colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS), mice on 4-wk HFD exhibited more severe colonic inflammation and developed more severe colitis compared with the LFD counterparts. HFD feeding resulted in higher production of mucosal pro-inflammatory cytokines, greater activation of the myosin light chain kinase (MLCK) tight junction regulatory pathway, and greater increases in mucosal barrier permeability in mice following TNBS induction. HFD feeding also induced gp91, an NADPH oxidase subunit, and promoted reactive oxygen species (ROS) production in both colonic epithelial cells and lamina propria cells. In HCT116 cell culture, palmitic acid or palmitic acid and TNF-α combination markedly increased ROS production and induced the MLCK pathway, and these effects were markedly diminished in the presence of a ROS scavenger. Taken together, these data suggest that HFD promotes colitis by aggravating mucosal oxidative stress, which rapidly drives mucosal inflammation and increases intestinal mucosal barrier permeability. NEW & NOTEWORTHY This study demonstrates high-fat diet feeding promotes colitis in a 2,4,6-trinitrobenzenesulfonic acid-induced experimental colitis model in mice. The underlying mechanism is that high-fat diet induces oxidative stress in the colonic mucosa, which increases colonic epithelial barrier permeability and drives colonic mucosal inflammation. These observations provide molecular evidence that diets high in saturated fats are detrimental to patients with inflammatory bowel diseases.

Expression and secretion of lipocortin 1 in gut inflammation are not regulated by pituitary-adrenal axis

1997 ◽  
Vol 273 (2) ◽  
pp. R623-R629 ◽  
Author(s):  
N. Vergnolle ◽  
C. Comera ◽  
J. More ◽  
M. Alvinerie ◽  
L. Bueno
Keyword(s):  
Culture Medium ◽  
Experimental Colitis ◽  
Myeloperoxidase Activity ◽  
Trinitrobenzenesulfonic Acid ◽  
Gut Inflammation ◽  
Adrenal Axis ◽  
Histological Damage ◽  
Anti Inflammatory ◽  
Pituitary Adrenal Axis

Lipocortin 1 is considered a mediator of the anti-inflammatory actions of glucocorticoids. We have shown that this protein is overexpressed and secreted during an experimental colitis induced by intraluminal injection of trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo regulation of lipocortin 1 expression and secretion in this model, either by glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h) animals or by pituitary factors using hypophysectomized animals. Inflammation was evaluated by measuring myeloperoxidase activity and by histological scoring of the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was studied by incubating colonic specimens in-culture medium. In the colon of TNBS-injected animals, cumulative histological damage scores were increased in adrenalectomized and decreased in dexamethasone-treated animals compared with control and hypophysectomized animals. The colons of all TNBS-injected animals (controls, adrenalectomized, dexamethasone treated, hypophysectomized) overexpressed and secreted lipocortin 1. In conclusion, the induction of lipocortin 1 overexpression and secretion during this colitis occurs independently of glucocorticoids or pituitary factors.

scholarly journals Effect of Forced Physical Activity on the Severity of Experimental Colitis in Normal Weight and Obese Mice. Involvement of Oxidative Stress and Proinflammatory Biomarkers

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1127 ◽  
Author(s):  
Jan Bilski ◽  
Agnieszka Mazur-Bialy ◽  
Dagmara Wojcik ◽  
Marcin Magierowski ◽  
Marcin Surmiak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treadmill Exercise ◽  
Experimental Colitis ◽  
Treadmill Running ◽  
Adaptation Period ◽  
Obese Mice ◽  
Trinitrobenzenesulfonic Acid ◽  
Sod Activity ◽  
Tnf Α ◽  
Colonic Blood Flow

Inflammatory bowel diseases are a heterogeneous group of disorders represented by two major phenotypic forms, Crohn’s disease and ulcerative colitis. Cross talk between adipokines and myokines, as well as changes in intestinal microcirculation, was proposed in pathogenesis of these disorders. C57BL/6 male mice were fed ad libitum for 12 weeks a standard (SD) or high-fat diet (HFD). After the adaptation period, two groups of animals fed SD or HFD were subjected to 6 weeks of the forced treadmill exercise and the experimental colitis was induced in both groups of sedentary and exercising mice fed SD and HFD by intra-colonic administration of 2,4,6-trinitrobenzenesulfonic acid. The disease activity index (DAI), colonic blood flow (CBF), the weight of animals, caloric intake, the mesenteric fad pad, the colonic oxidative stress markers malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) activity and intestinal expression and protein content of proinflammatory markers were evaluated. Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF and exacerbated in those fed a HFD. The contents of MDA, GSH, and SOD activity were significantly increased in both SD and HFD fed mice with treadmill exercise as compared with sedentary mice. In sedentary HFD mice a significant increase in the intestinal oxidative stress parameters and mucosal expression of IL-1β, TNF-α, IL-17, IFNγ, IL-6, and IL-10 protein were observed and these effects were aggravated in mice subjected to forced treadmill exercise. The mucosal expression of mRNA for TNF-α, IL-1β, iNOS, COX-2, SOD-1, SOD-2, GPx mRNAs, and the hypoxia inducible factor (HIF)-1α protein expression were upregulated in colonic mucosa of treadmill exercising HFD mice with colitis compared with those without exercise. We conclude that forced treadmill running exacerbates the severity of colonic damage in obese mice due to a fall in colonic microcirculation, an increase in oxidative stress, and the rise in expression and activity of proinflammatory biomarkers.

Effect of mangiferin on NF-κB expression in experimental colitis induced by trinitrobenzenesulfonic acid in rats

2015 ◽  
Vol 67 ◽  
pp. 40-41
Author(s):  
Marta Szandruk ◽  
Beata Nowak ◽  
Agnieszka Matuszewska ◽  
Anna Czarny ◽  
Ewa Zaczyńska ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
Trinitrobenzenesulfonic Acid
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