Local corticosterone production and angiotensin-I converting enzyme shedding in a mouse model of intestinal inflammation

Abstract

AIM: 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 mu mol/L angiotensin II, 1, 10 or 100 mu mol/L captopril or 1, 10 or 100 mu mol/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 mu mol/L (0.97 +/- 0.21 ng/mg protein vs 0.40 +/- 0.09 ng/mg protein, P = 0.036). CONCLUSION: Intestinal ACE shedding is increased by DSS-induced intestinal inflammation and parallels local corticosterone production. ACE product angiotensin. stimulates corticosterone formation in healthy intestine.