title: Local corticosterone production and angiotensin-I converting enzyme shedding in a mouse model of intestinal inflammation.
abstract: OBJECTIVE
  To investigate local corticosterone production and angiotensin-I converting enzyme (ACE) protein expression and their interaction in healthy and inflamed intestine.
  
  
  METHODS
  Acute intestinal inflammation was induced to six weeks old male Balb/c mice by administration of either 3% or 5% dextran sodium sulfate (DSS) in drinking water for 7 d (n = 12 in each group). Healthy controls (n = 12) were given tap water. Corticosterone production and ACE protein shedding were measured from ex vivo incubates of the small and large intestine using EIA and ELISA, respectively. Morphological changes of the intestinal wall were assessed in hematoxylin-eosin stained tissue preparations of jejunum and distal colon. Effects of angiotensin II, captopril and metyrapone on corticosterone production was assessed by incubating pieces of small intestine of healthy mice in the presence of 0.1, 1 or 10 μmol/L angiotensin II, 1, 10 or 100 μmol/L captopril or 1, 10 or 100 μmol/L metyrapone solutions and measuring corticosterone released to the incubation buffer after 90 min (n = 5 in each group).
  
  
  RESULTS
  Both concentrations of DSS induced inflammation and morphological changes in large intestines but not in small intestines. Changes were observed as distortions of the crypt structure, mucosal erosion, immune cell infiltration to the mucosa and submucosal edema. Ex vivo corticosterone production (2.9 ± 1.0 ng/mL vs 2.0 ± 0.8 ng/mL, P = 0.034) and ACE shedding (269.2 ± 97.1 ng/mL vs 175.7 ± 52.2 ng/mL, P = 0.016) were increased in small intestines in 3% DSS group compared to the controls. In large intestine, corticosterone production was increased compared to the controls in both 3% DSS (229 ± 81 pg/mL vs 158 ± 30 pg/mL, P = 0.017) and 5% DSS groups (366 ± 163 pg/mL vs 158 ± 30 pg/mL, P = 0.002). Large intestine ACE shedding was increased in 5% DSS group (41.5 ± 9.0 ng/mL vs 20.9 ± 5.2 ng/mL, P = 0.034). Angiotensin II treatment augmented corticosterone production in small intestine at concentration of 10 μmol/L (0.97 ± 0.21 ng/mg protein vs 0.40 ± 0.09 ng/mg protein, P = 0.036).
  
  
  CONCLUSIONS
  Intestinal ACE shedding is increased by DSS-induced intestinal inflammation and parallels local corticosterone production. ACE product angiotensin II stimulates corticosterone formation in healthy intestine.
authors.affiliation: Hanne Salmenkari, Tomi Issakainen, Heikki Vapaatalo, Riitta Korpela, Faculty of Medicine, Pharmacology, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Hanne
authors.initials: H
authors.lastname: Salmenkari
authors.affiliation: Hanne Salmenkari, Tomi Issakainen, Heikki Vapaatalo, Riitta Korpela, Faculty of Medicine, Pharmacology, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Tomi
authors.initials: T
authors.lastname: Issakainen
authors.affiliation: Hanne Salmenkari, Tomi Issakainen, Heikki Vapaatalo, Riitta Korpela, Faculty of Medicine, Pharmacology, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Vapaatalo
authors.affiliation: Hanne Salmenkari, Tomi Issakainen, Heikki Vapaatalo, Riitta Korpela, Faculty of Medicine, Pharmacology, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Korpela
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D003345:Corticosterone / Q000378:metabolism*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004751:Enteritis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007579:Jejunal Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011725:Pyridines; D000804:Angiotensin II; C013109:metapyrone; D016264:Dextran Sulfate; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D003345:Corticosterone
keywords: Angiotensin-I converting enzyme; Dextran sodium sulfate; Inflammation; Intestine; Local corticosterone