ER Stress Promotes Intestinal Inflammation By Up-regulating The Expression Gro-? And IL-8 Via P38 MAPK Pathway In Crohn's Disease

Introduction:The purpose of this study was to investigate whether endoplasmic reticulum stress can promote the formation of intestinal inflammation in Crohn's disease(CD)by regulating the expression of chemokines through the study of gross specimens of patients with CD and vitro experiments.Methods:1.Pathological colon specimens of patients undergoing surgical treatment for CD in our hospital were collected,and the protein expression of endoplasmic reticulum stress marker Grp78 and chemokine IL-8 in the intestinal tissues of CD patients was detected by immunohistochemistry,and compared with the paracancerous colon specimens of patients with colon cancer.2.we cultured colon cancer epithelial cell HCT116.HCT116 cells were treated with different concentrations of tunicamycin to induce endoplasmic reticulum stress.Or HCT116 cells were pre-incubated with IRE1? inhibitor(STF083010),a selective eIF-2? dephosphorylation inhibitor(Salubrinal)and p38 MAPK inhibitor(SB203580)for 1h to blocking IRE1-XBP1?PERK-eIF2??P38 MAPK signaling pathways,followed by appropriate concentration of tunicamycin treatment.3.The protein pression of Grp78 was measured by Western Blot,and the mRNA expression of the chemokines Gro-?and IL-8 were detected by q-RT-PCR,and the protein expression of IL-8 in the cell supernatant was detected by ELISA.Results:1.compared with the paracancerous colon specimens of patients with colon cancer,expression levels of Grp78 and IL-8 were significantly upregulated in intestinal tissues of CD.2.With the increased concentration of tunicamycin,the expression of Grp78 protein increased,and the expression of Gro-? and IL-8 were also up-regulated,which were most obvious at 5?g/mL.3.Blocking IRE1-XBP1 and PERK-eIF2? pathway did not affect the expression of Grp78 and the up-regulation of Gro-? and IL-8.4.P38 MAPK inhibitor SB203580 significantly prevented the pression of Gro-? and IL-8 mRNA and IL-8 protein induced by tunicamyin.Conclusions:1.ER stress and IL-8 are involved in the formation of intestinal inflammation in CD patients.2.Endoplasmic reticulum stress can promote intestinal inflammation by up-regulating the expression of Gro-? and IL-8,possibly by activating the p38 MAPK pathway.