Expression And Clinical Significance Of MFG-E8 And NF-κBp65 In Intestinal Mucosa Of Patients With Ulcerative Colitis

Backgroud:Ulcerative colitis(UC) is a nonspecific chronic inflammatory bowel disease, which mainly affects the mucosal layer of rectum and colon. Patients usually present with abdominal pain, diarrhea mixed with blood and mucus. The etiology and pathogenesis of UC have not been fully elucidated. Currently, we considered that the genetic, environmental, and autoimmune factors play an important role in the pathogenesis of the disease.Milk fat globule-epidermal growth factor 8(MFG-E8) is a lactadherin, which secreted from various cells,in including mammary epithelial cells. Several studies of animal models revealed that MFG-E8 played an important role in regulation of intestinal inflammation and repair of intestinal mucosa. In DSS model MFG-E8 expression was dramatically reduced during the acute phase of the disease, while it gradually became elevated during the regeneration phase after DSS in water intake was stopped and finally returned to a normal level when the disease was abrogated. Similar time-course changes of MFG-E8 expression were also found in a trinitrobenzene sulfonic acid(TNBS)-induced colitis model. A recent study suggested that pre-treatment with recombinant MFG-E8(rMFG) and observed its beneficial effect to inhibit intestinal inflammation. These studies demonstrated that MFG-E8 play an important role in Regulation of intestinal inflammation. In addition, recent study revealed that rMFG-E8 administered during the recovery phase of DSS-induced colitis in mouse could attenuate inflammation, which demonstrated that MFG-E8 contribute to healing of injured colonic mucosa.Nuclear Factor kappa B(NF-κB) was identified as an important factor in the regulation of gene transcription. NF-κB is involved in gene regulatory process of pathophysiology in cell apoptosis, tumor cell metastasis and Many immune inflammatory responses, also it palys an important role in regulation of intestinal inflammation. NF-κB constitutes the main regulation of Immune cell communication mechanism and cytokine production imbalance in the pathogenesis of UC. A study clearly demonstrated that NF-κB is not just expressed but is also in a state of activation in mucosal macrophages and epithelial cells in UC patients. The amount of activated NF-κB correlated significantly with the severity of intestinal inflammation.The study of animal model demonstrated that MFG-E8 down-regulated proinflammatory cytokines through αvβ3 integrin-medicated NF-κB inhibition. However, so far, we have not clear whether there is a correlation between MFG-E8 and NF-κB in patients with UC.Objectives:To explore the expression and clinical significance of MFG-E8 and NF-κBp65 in intestinal mucosa of patients with UC.Methods:The expression of MFG-E8 and NF-kBp65 in intestinal mucosa of UC patients and normal controls was detected by immunohistochemistry. The clinical severity of UC patients was classified according to the modified truelove and witts severity indexing and disease activity degree was calculated according to the modified Mayo scoring system, endoscopic grading was classified according to Baron standards, histopathological grading was classified according to Truelove-Richards standards.Results:MFG-E8,NF-κBp65 are present in the intestinal epithelial cell and crypt epithelium, UC patients Group showed less staining for MFG-E8 than control group. In contrast, NF-κBp65 showed strong positive staining in UC patients Group.The difference between expression of the two proteins in UC group and in control group has statistical significance(P<0.05). The positive expression rate of MFG-E8 in the ntestinal mucosa of UC patients and normal control group was 6.3%, 26.1%, those of NF-κB p65 was 93.8%, 69.6%. The positive number of MFG-E8 expression was gradually reduced by disease severity, endoscopic and pathological grades, and with the severity of the disease, the positive number of MFG-E8 expression decreased gradually,mild higher than severe(P<0.05). However, the positive number of NF-κBp65 expression was gradually increased with the severity of the disease, severe higher than mild(P<0.05), which of endoscopic and histopathological III grade was higher than I grade(P<0.05). The relationship between expressions of MFG-E8 and NF-κBp65 was negatively correlated(r=-1.000 P<0.01) in UC.Conclusion:1. In UC group The expression rate of MFG-E8 and NF-κBp65 closely related to the severity of the disease and the stage of the disease.2. The positive expression rate of MFG-E8 and NF-κBp65 level in UC patients is closely correlated with endoscopic grading and pathological grading.3.The expression of MFG-E8 in intestinal mucosa of UC patients is negatively correlated with NF-κBp65, MFG-E8 and NF-κBp65 may participate in the development and progression of the inflammation in UC, and their combined detection can help diagnose the disease severity.