Basic-alimentary tractNF-κB activation by oxidative stress and inflammation suppresses contractility in colonic circular smooth muscle cells☆
Section snippets
Induction of colonic inflammation
Acute colonic inflammation was induced by mucosal exposure to ethanol and acetic acid as described previously.22, 32, 33 Briefly, on day 1, the dogs were given an intravenous injection of 30 μg/kg neostigmine to induce defecation. Then they were anesthetized with 150 mg IM Telazol (Elkins-Sinn, Inc., Cherry Hill, NJ). An intraluminal tube with side holes in the first 5-cm length was advanced to the ascending colon, about 50 cm from the anal margin. The colon was cleansed by flushing it with 700
Clinical symptoms and mucosal injury
All dogs developed diarrhea within 24 hours after the induction of inflammation. The mucosa appeared diffusely inflamed, and there were scattered ulcerations and exudates over the mucosal surface. The mean morphology score in the inflamed colon, 4.2 ± 0.4 (n = 4), was significantly greater than that in the normal colon, 0.4 ± 0.2 (n = 7).
NF-κB DNA binding in cells from the normal and the inflamed colon
The mean relative value of NF-κB DNA binding in smooth muscle cells from the inflamed colon, (lanes 4–6, Figure 1) was 6.2-fold greater than that in cells
Discussion
Our findings show that inflammation as well as oxidative stress with H2O2 activates NF-κB in canine colonic circular smooth muscle cells, resulting in suppression of their contractility. The nuclear transcription factor NF-κB in colonic smooth muscle cells is composed of subunits p65, p50, and c-Rel. Using EMSA and Western immunoblotting, we did not find any evidence for the presence of p52 in these cells. However, we cannot rule out the possibility that the human antibody for p52 that we used
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Supported in part by NIDDK grant DK32346 (to S.K.S.).
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The authors thank the late Dr. You-Gang Lin for his help with immunofluorescence imaging in this study.