Abstract
Recently the role of Parkinson’s disease 7 (PARK7) was studied in gastrointestinal diseases, however, the complex role of PARK7 in the intestinal inflammation is still not completely clear. Expression and localization of PARK7 were determined in the colon biopsies of children with inflammatory bowel disease (IBD), in the colon of dextran sodium sulphate (DSS) treated mice and in HT-29 colonic epithelial cells treated with interleukin (IL)-17, hydrogen peroxide (H2O2), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β or lipopolysaccharide (LPS). Effect of PARK7 on the synthesis of IBD related cytokines was determined using PARK7 gene silenced HT-29 cells and 3,4,5-trimethoxy-N-(4-(8-methylimidazo(1,2-a)pyridine-2-yl)phenyl)benzamide (Comp23)—compound increasing PARK7 activity—treated mice with DSS-colitis. PARK7 expression was higher in the mucosa of children with Crohn’s disease compared to that of controls. While H2O2 and IL-17 treatment increased, LPS, TNF-α or TGF-β treatment decreased the PARK7 synthesis of HT-29 cells. PARK7 gene silencing influenced the synthesis of IL1B, IL6, TNFA and TGFB1 in vitro. Comp23 treatment attenuated the ex vivo permeability of colonic sacs, the clinical symptoms, and mucosal expression of Tgfb1, Il1b, Il6 and Il10 of DSS-treated mice. Our study revealed the role of PARK7 in the regulation of IBD-related inflammation in vitro and in vivo, suggesting its importance as a future therapeutic target.
Highlights
The role of Parkinson’s disease 7 (PARK7) was studied in gastrointestinal diseases, the complex role of PARK7 in the intestinal inflammation is still not completely clear
While IL-17 or H 2O2 treatment increased, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β or LPS treatment decreased the amount of PARK7 (Fig. 2c,d,f,g)
Recently our research group demonstrated the role of PARK7 in the maintenance of duodenal mucosal integrity of children with coeliac d isease[12,13], and Di N arzo[23] and Zhang et al.[24] investigated the amount of PARK7 in the plasma and intestine of adult patients with inflammatory bowel disease (IBD), respectively
Summary
The role of Parkinson’s disease 7 (PARK7) was studied in gastrointestinal diseases, the complex role of PARK7 in the intestinal inflammation is still not completely clear. Expression and localization of PARK7 were determined in the colon biopsies of children with inflammatory bowel disease (IBD), in the colon of dextran sodium sulphate (DSS) treated mice and in HT-29 colonic epithelial cells treated with interleukin (IL)-17, hydrogen peroxide (H2O2), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β or lipopolysaccharide (LPS). Effect of PARK7 on the synthesis of IBD related cytokines was determined using PARK7 gene silenced HT-29 cells and 3,4,5-trimethoxy-N-(4-(8-methylimidazo(1,2-a)pyridine-2-yl)phenyl)benzamide (Comp23)— compound increasing PARK7 activity—treated mice with DSS-colitis. Our study revealed the role of PARK7 in the regulation of IBD-related inflammation in vitro and in vivo, suggesting its importance as a future therapeutic target. In this study we report the presence, regulation and role of PARK7 in the pathomechanism of mucosal inflammation using tissue samples of therapy-naive children with IBD, and in vitro and in vivo experimental models of colitis. Our study suggests the possible therapeutic relevance of PARK7 in the treatment of IBD
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