Abstract

Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentrations of IL-1β, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1β and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC.

Highlights

  • Ulcerative colitis is an idiopathic, chronic inflammatory disease of the colon, most commonly affecting people aged 30 to 40 years [1,2]

  • And E, tumor necrosis factoralpha (TNF-a) increased the levels of IL-1b and IL-6 compared to the control. Western blotting confirmed these findings as TNF-a increased the expressions of IL-1b and IL-6 (Figure 1F). These findings indicated that TNF-a induced inflammatory injury in Interstitial cells of Cajal (ICC) by decreasing cell viability and increasing apoptosis and secretion of pro-inflammatory cytokines

  • We assessed the effects of TNF-a on viability and apoptosis of ICC, and on the levels of IL-1b, IL-6, stem cell factor (SCF), ghrelin, endothelin-1, and substance P in ICC

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Summary

Introduction

Ulcerative colitis is an idiopathic, chronic inflammatory disease of the colon, most commonly affecting people aged 30 to 40 years [1,2]. Ulcerative colitis is characterized by mucosal inflammation of the rectum and colon. Major symptoms include bloody diarrhea, fatigue, abdominal cramps, urgency, and fever [4,5,6]. Ulcerative colitis is most prevalent in Europe (505 per 100.000 persons), followed by Canada (248 per 100.000 persons), and the USA (214 per 100.000 persons). Treatments of ulcerative colitis include aminosalicylates for mild to moderate disease, topical and systemic steroids for disease flares, and immunosuppressants and biological drugs for moderate to severe disease. Colectomy is required for patients with refractory disease or colonic neoplasia [3]; effective control of ulcerative colitis still remains difficult

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