title: Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat, 13110, Kuwait.
authors.forename: Maitham A
authors.initials: MA
authors.lastname: Khajah
authors.affiliation: Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat, 13110, Kuwait.
authors.forename: Maryam M
authors.initials: MM
authors.lastname: Fateel
authors.affiliation: Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat, 13110, Kuwait.
authors.forename: Kethireddy V
authors.initials: KV
authors.lastname: Ananthalakshmi
authors.affiliation: Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat, 13110, Kuwait.
authors.forename: Yunus A
authors.initials: YA
authors.lastname: Luqmani
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C000715471:Mas1 protein, mouse; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D016264:Dextran Sulfate; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)