Treatment with novel AP-1 and NF-B inhibitors restores the colonic endocrine cells to normal levels in rats with DSS-induced colitis

Abstract

The aim of this study was to determine the effects of two anti-inflammatory agents on the abnormalities in colonic endocrine cells in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced in male Wistar rats (n=45) using DSS; a further 15 rats without colitis were included in a healthy control group. The animals with DSS-induced colitis were randomly divided into 3 treatment groups as follows: i) DSS group, rats were treated with 0.5 ml of 0.5% carboxymethyl cellulose (CMC); ii) DSSG group, rats were treated with 3-[(dodecylthiocarbonyl)methyl]glutarimide (DTCMG), a novel activator protein 1 (AP-1) inhibitor, 20 mg/kg in CMC; and iii) DSSQ group, rats were treated with dehydroxymethylepoxyquinomicin, a nuclear factor B (NF-B) inhibitor, 15 mg/kg in CMC. The treatments were administered intraperitoneally, twice daily for 5 days, after which the animals were sacrificed and tissue samples from the colon were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), enteroglucagon, pancreatic polypeptide (PP), somatostatin, leukocytes, B/T lymphocytes, B lymphocytes, T lymphocytes, macrophages/monocytes and mast cells. The densities of these endocrine and immune cells were quantified by computeraided image analysis. The densities of CgA-, serotonin-, PYY-and enteroglucagon-producing cells were significantly higher, and those of PP-and somatostatin-producing cells were significantly lower in the DSSG, DSSQ and control groups than in the DSS group. The densities of all the immune cells were lower in the DSSG, DSSQ and control groups than in the DSS group. The densities of all endocrine cell types and immune cells in both the DSS groups treated with antiinflammatory agents were restored to control levels. In conclusion, our data demonstrate that there is an interaction between endocrine and immune cells during inflammation. This interaction with subsequent changes in endocrine cells is responsible for the clinical manifestation of colitis symptoms.