angiotensin-i and Colitis

To explore the treatment effect of mica on 2,4,6-trinitrobenzenesulfonic acid solution- (TNBS-) induced colitis in mice.. Thirty male BALB/C mice were randomly divided into the control group, the TNBS group, and the mica group. Control mice were treated with saline solution. Experimental colitis was induced by TNBS (250 mg/kg/d) in the TNBS group and the mica group. After modeling, the mica group was treated with mica (180 mg/kg/d) for 3 days, while the TNBS group continued the treatment with TNBS. All solutions were injected intrarectally. During treatment, body weight and mice activity were monitored daily. After treatment, the colon tissues of mice were collected; angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), angiotensin 1-7 (Ang (1-7)), IL-17A, and IL-10 expression was analyzed by ELISA and immunohistochemistry.. Food intake, activity, and body weight gradually decreased in the TNBS group compared to the control group and the mica group (all. Mica can alleviate TNBS-induced colitis in mice by regulating the inflammation process; it reduces Ang II and IL-17A and increases ACE2, IL-10, and Ang (1-7).

Topics: Aluminum Silicates; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Colitis; Eating; Enzyme-Linked Immunosorbent Assay; Interleukin-10; Interleukin-17; Male; Mice; Peptide Fragments; Trinitrobenzenesulfonic Acid

We recently demonstrated Ang 1-7 reduced inflammation in the dextran sulfate sodium (DSS) colitis model. In this study we examined the effect of Ang 1-7 on modulation of plasma levels of selected cytokines and chemokines and immune cell effector functions (apoptosis, chemotaxis and superoxide release) in vitro. The degree of neutrophil recruitment to the colon was assessed by immunofluorescence and myeloperoxidase activity. Daily Ang 1-7 treatment at 0.01 mg/kg dose which previously ameliorated colitis severity, showed a significant reduction in circulating levels of several cytokines and chemokines, and neutrophil recruitment to the colonic tissue. It also significantly enhanced immune cell apoptosis, and reduced neutrophil chemotaxis and superoxide release in vitro. In contrast, daily administration of the Ang 1-7R antagonist A779 which previously worsened colitis severity showed significant up-regulation of specific mediators. Our results demonstrate a novel anti-inflammatory action of Ang 1-7 through modulation of plasma levels of cytokines/chemokines and immune cell activity.

Topics: Angiotensin I; Angiotensin II; Animals; Anti-Inflammatory Agents; Apoptosis; Cell Movement; Chemokines; Chemotaxis; Colitis; Colon; Cytokines; Dextran Sulfate; Immunity, Cellular; Immunomodulation; Mice; Mice, Inbred BALB C; Models, Animal; Neutrophils; Peptide Fragments; Renin-Angiotensin System; Superoxides

There is evidence to support a role for angiotensin (Ang) 1-7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study.. The colonic expression/activity profile of ACE2, Ang 1-7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1-7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model.. Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1-7 treatment (0.01-0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1-7 treatment.. Our results indicate important anti-inflammatory actions of Ang 1-7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.

Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Animals; Anti-Inflammatory Agents; Colitis; Dextran Sulfate; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Female; Male; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Peptide Fragments; Peptidyl-Dipeptidase A; Proto-Oncogene Mas; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptors, G-Protein-Coupled

A 15-year retrospective review was undertaken to evaluate the operative outcomes of patients with indeterminate colitis who were referred for rectal-sparing operations. Review of 95 consecutive patients operated for ulcerative colitis (UC) or indeterminate colitis (IC) revealed characteristics of IC in 13 patients. In the group as a whole, there were 45 females and 50 males; the average age was 33. A total of 64 patients had ileoanal pull-through (IAA). Analysis revealed that four of these patients had IC revealed by findings before operation in three patients and following the first stage of operation in one patient. Three of these four patients have subsequently required permanent ileostomy. Six patients who underwent IAA have subsequently demonstrated signs and symptoms of Crohn's disease (CD). All six have subsequently required ileostomy. Overall 10 patients with CD underwent IAA, and nine have required permanent ileostomy. Fourteen patients had ileorectal anastomosis (IRA) for UC or IC. IRA was performed for patients with IC in nine cases, and five patients with UC elected this operative option. Indications for IRA in patients with UC included obesity, 2; mental retardation, 1; advanced age, 1; and patient preference, 1. Of the patients with IC who underwent IRA, two have subsequently shown signs and symptoms of Crohn's disease. Overall, 14 of 14 patients who had IRA still have functioning IRA. None has required ileostomy. The poor results in patients with UC or IC subsequently shown to have CD have caused us to change our operative approach in patients with any question in the diagnosis of UC.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anastomosis, Surgical; Angiotensin I; Angiotensin II; Colectomy; Colitis; Colitis, Ulcerative; Colon; Crohn Disease; Elective Surgical Procedures; Female; Follow-Up Studies; Humans; Ileostomy; Intestinal Mucosa; Male; Proctocolectomy, Restorative; Rectum; Retrospective Studies; Treatment Outcome

To define a potential role for the angiotensin system in Crohn's colitis, the colonic mucosal levels of angiotensin I and II were measured in endoscopic biopsy samples from patients with active Crohn's colitis (n = 20), ulcerative colitis (n = 13), other forms of colitis (n = 3), and normal controls (n = 17). Colonic mucosal levels of angiotensin I and II were greater in patients with Crohn's colitis than in normal subjects (p less than 0.001 and p less than 0.001, respectively). Mucosal levels of angiotensin I and II were also higher in Crohn's colitis than in ulcerative colitis (p less than 0.001 and p less than 0.001, respectively), and levels of angiotensin II were higher in Crohn's than in other forms of colitis (p = 0.014). Mucosal levels of angiotensin I and II correlated well with the degree of macroscopic inflammation in Crohn's colitis (r = 0.86, p less than 0.001 and r = 0.68, p less than 0.001, respectively). Mucosal levels of angiotensin I correlated fairly well with the Crohn's Disease Activity Index (r = 0.46, p less than 0.05) while angiotensin II levels correlated poorly. These studies suggest that angiotensin I and II may have a role in the inflammation associated with Crohn's colitis.

Topics: Angiotensin I; Angiotensin II; Chromatography, High Pressure Liquid; Colitis; Colitis, Ulcerative; Colon; Colonoscopy; Crohn Disease; Humans; Intestinal Mucosa; Peptidyl-Dipeptidase A; Sigmoidoscopy; Single-Blind Method