Immunomodulatory role of Parkinson's disease 7 in inflammatory bowel disease

被引：15

作者：

Lippai, Rita ^{[1
]}

Veres-Szekely, Apor ^{[1
,2
]}

Sziksz, Erna ^{[1
]}

Iwakura, Yoichiro ^{[3
,4
]}

Pap, Domonkos ^{[2
]}

Rokonay, Reka ^{[1
]}

Szebeni, Beata ^{[2
]}

Lotz, Gabor ^{[5
]}

Beres, Nora J. ^{[1
]}

Cseh, Aron ^{[1
]}

Szabo, Attila J. ^{[1
,2
]}

Vannay, Adam ^{[1
,2
]}

机构：

[1] Semmelweis Univ, Dept Pediat 1, 54 Bokay St, H-1083 Budapest, Hungary

[2] ELKH SE Pediat & Nephrol Res Grp, Budapest, Hungary

[3] Tokyo Univ Sci, Res Inst Biomed Sci, Tokyo, Japan

[4] Tokyo Univ Sci, Ctr Anim Dis Models, Res Inst Sci & Technol, Tokyo, Japan

[5] Semmelweis Univ, Dept Pathol 2, Budapest, Hungary

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

关键词：

OXIDATIVE STRESS; CROHNS-DISEASE; PEDIATRIC-PATIENTS; DJ-1; EXPRESSION; PROTEIN; SUPPRESSION; MECHANISMS; REGULATOR; DAMAGE;

D O I：

10.1038/s41598-021-93671-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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)-alpha, transforming growth factor (TGF)-beta 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-alpha or TGF-beta 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.

引用

页数：14

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