Role of leptin and TNF-α in energy metabolism regulation in patients with inflammatory bowel disease

AbstractRecently 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.

Download Full-text

Cytokines in canine inflammatory bowel disease

Polish Journal of Veterinary Sciences ◽

10.2478/pjvs-2013-0025 ◽

2013 ◽

Vol 16 (1) ◽

pp. 165-171 ◽

Cited By ~ 13

Author(s):

A. Kołodziejska-Sawerska ◽

A. Rychlik ◽

A. Depta ◽

M. Wdowiak ◽

M. Nowicki ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Mrna Expression ◽

Lamina Propria ◽

Bowel Disease ◽

Unknown Etiology ◽

Tnf Α ◽

Chronic Enteropathies ◽

Inflammatory Bowel ◽

Ifn Γ

Abstract Canine inflammatory bowel disease is a group of chronic enteropathies characterized by persistent or recurring gastric symptoms with an unknown etiology which are related to histopathological changes in the mucosa of the small and large bowel in the form of cellular infiltration in the mucosal lamina propria. Recent years have witnessed a growing number of investigations into the role of the immune system and, in particular, cytokines in the development of IBD. In this article, the expression of pro-inflammatory (IL-1, IL-2, IL-5, IL-6, IL-12, IL-18, IFN-γ, TNF-α) and anti-inflammatory cytokines (IL-4, IL-10) was compared in canine patients with IBD based on clinical presentation, breed, lamina propria cell infiltrate and histopathological grade. Only selected studies confirmed higher mRNA expression levels of cytokines IL-2, IL-4, IL-5, IL-12p40, IFN-γ, TNF-α and TGF-β in dogs with IBD in comparison with healthy subjects. GSD were strongly represented in most study populations. Dogs with LPE were characterized by elevated levels of IL-1α, IL-1β, IL-2, IL-5, IL-6, IL-12, TNF-α, TGF-β. The present studies of canine patients with LPC revealed the mRNA expression of cytokines IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p35, IL-12p40, IFN-γ, TNF-α, TGF-β. In the reviewed studies, the progression of IBD was not accompanied by changes in the mRNA expression of IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-18, TNF-α, IFN-γ or TGF-β.

Download Full-text

STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease

Clinical Epigenetics ◽

10.1186/s13148-021-01101-w ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Ya-Li Yu ◽

Meng Chen ◽

Hua Zhu ◽

Ming-Xing Zhuo ◽

Ping Chen ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Target Genes ◽

Dextran Sulfate ◽

Rna Seq ◽

Acute Colitis ◽

Tnf Α ◽

Inflammatory Bowel ◽

Inducible Protein

Abstract Background The aetiology of inflammatory bowel disease (IBD) is related to genetics and epigenetics. Epigenetic regulation of the pathogenesis of IBD has not been well defined. Here, we investigated the role of H3K27ac events in the pathogenesis of IBD. Based on previous ChIP-seq and RNA-seq assays, we studied signal transducer and activator of transcription 1 (STAT1) as a transcription factor (TF) and investigated whether the STAT1–EP300–H3K27ac axis contributes to the development of IBD. We performed ChIP-PCR to investigate the interaction between STAT1 and H3K27ac, and co-IP assays were performed to investigate the crosstalk between STAT1 and EP300. Results Lymphocyte cytosolic protein 2 (LCP2) and TNF-α‐inducible protein 2 (TNFAIP2) are target genes of STAT1. p-STAT1 binds to the enhancer loci of the two genes where H3K27ac is enriched, and EP300 subsequently binds to regulate their expression. In mice with dextran sulfate sodium (DSS)-induced acute colitis, an EP300 inhibitor significantly inhibited colitis. Conclusions p-STAT1 and EP300 promote TNFAIP2 and LCP2 expression through an increase in H3K27ac enrichment on their enhancers and contribute to the pathogenesis of chronic inflammation. Graphic abstract

Download Full-text

The role of osteopontin (OPN/SSP1) gene variants in inflammatory bowel disease

Zeitschrift für Gastroenterologie ◽

10.1055/s-0029-1241334 ◽

2009 ◽

Vol 47 (09) ◽

Author(s):

J Glas ◽

J Seiderer ◽

HP Török ◽

B Göke ◽

T Ochsenkühn ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Gene Variants ◽

Inflammatory Bowel

Download Full-text

Nutrition in inflammatory bowel disease

Orvosi Hetilap ◽

10.1556/oh.2009.28599 ◽

2009 ◽

Vol 150 (18) ◽

pp. 839-845 ◽

Cited By ~ 2

Author(s):

János Banai

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fast Food ◽

Optimal Growth ◽

Developed Countries ◽

Aetiological Factor ◽

Artificial Nutrition ◽

Food Preservatives ◽

Inflammatory Bowel

Aetiology of inflammatory bowel disease (IBD) is complex and probably multifactorial. Nutrition has been proposed to be an important aetiological factor for development of IBD. Several components of the diet (such as sugar, fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were examined as possible causative agents for IBD. According to some researchers infant feeding (breast feeding) may also contribute to the development of IBD. Though the importance of environmental factors is evidenced by the increasing incidence in developed countries and in migrant population in recent decades, the aetiology of IBD remained unclear. There are many theories, but as yet no dietary approaches have been proved to reduce the risk of developing IBD. The role of nutrition in the management of IBD is better understood. The prevention and correction of malnutrition, the provision of macro- and micronutrients and vitamins and the promotion of optimal growth and development of children are key points of nutritional therapy. In active disease, the effective support of energy and nutrients is a very important part of the therapy. Natural and artificial nutrition or the combination of two can be choosen for supporting therapy of IBD. The author summarises the aetiological and therapeutic role of nutrition in IBD.

Download Full-text