Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease

Andersen, Vibeke; Christensen, Jane; Ernst, Anja; Jacobsen, Bent Ascanius; Tjønneland, Anne; Krarup, Henrik; Vogel, Ulla

doi:10.3748/wjg.v17.i2.197

Cited by 80 publications

(61 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conceivably, genes involved in the NF-κB pathway are interesting candidate genes for chronic inflammatory disorders, including CD and UC. In 2 mouse models of colitis, although not the same physiological condition as in humans, a strong linkage has been observed between a polymorphism in the NFKB1 gene and the susceptibility to UC and CD [37][38][39]. However, given that some authors have suggested that the role of NFKB in the regulation of apoptosis is not yet defined, our group studied its levels in various stages of CD.…”

Section: Discussionmentioning

confidence: 99%

Different Genetic Expression Profiles of Oxidative Stress and Apoptosis-Related Genes in Crohn’s Disease

et al. 2018

View full text Add to dashboard Cite

Background/Aims: Increased oxidative stress and decreased immune cell apoptosis have been reported to be important factors in the pathogenesis of Crohn’s disease (CD). Our aim was to characterize the genetic expression of molecules implicated in the regulation of oxidative stress and apoptosis in peripheral white mononuclear cells of 18 healthy volunteers (controls) and 20 patients at the onset of CD (active CD [aCD]): 10 who achieved remission (inactive CD [iCD]) and 10 who did not present a complete and deep response to treatment (aCD-T). Methods: mRNA expression was measured by the Agena MassARRAY quantitative gene expression analysis application. The genes analyzed were Fas-receptor (FASR), Fas-ligand (FASL), signal transducer and activator of transcription 1 (STAT1), nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB1), apoptosis signal-regulating kinase 1 (ASK1), serine/threonine-protein kinase H1 (PSKH1), ATP-binding cassette sub-family B1 (ABCB1) and peptidylprolyl isomerase D (PPID). Results: During a CD flare, we found specific upregulated expression of the genes STAT1 and PSKH1, whereas ABCB1 and FASL were downregulated. In the patients with iCD, FASR and NFKB1 were upregulated. The expression levels of NFKB1, STAT1 and ABCB1 did not show any difference in patients with aCD at the onset of the disease and after treatment (aCD-T). The expression levels of PPID and ASK1 did not show any differences in the patients with aCD, iCD and the controls. We have also reviewed the cellular function and role of these genes in CD. Conclusions: These findings contribute to improving the understanding of the pathogenesis of CD and highlight potential genes involved.

show abstract

Section: Discussionmentioning

confidence: 99%

Different Genetic Expression Profiles of Oxidative Stress and Apoptosis-Related Genes in Crohn’s Disease

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Excess or inappropriate activation of NF-B has been observed in IBD patients and experimental IBD animal models (2). It has been demonstrated that the blockade of NF-B activation with flavanoid agents might be an effective strategy in abrogating experimental IBD (6,26).…”

Section: Discussionmentioning

confidence: 99%

The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis

Ren

Sun

Deng

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Cardamonin is a naturally occurring chalcone with strong anti-inflammatory activity. However, the direct effect of cardamonin on intestinal inflammation remains elusive. In the present study, we found that cardamonin markedly ameliorated dextran sulfate sodium-induced mouse body weight loss, diarrhea, colon shortening, spleen swelling, and histological damage, which correlated with a decline in the activity of myeloperoxidase and the production of nitric oxide, tumor necrosis factor-α and interleukin-6 in the colon. The upregulation of toll-like receptor 4 after dextran sulfate sodium treatment was associated with an increase in the activation of myeloid differentiation factor 88, interleukin-1 receptor-associated kinase-1, nuclear factor-κB (NF-κB) p65, inhibitor κBα, and inhibitor κB kinase-α/β, as well as the mitogen-activated protein kinase molecules of extracellular signal-regulated kinase and c-Jun NH2-terminal kinase, and this upregulation was reversed by cardamonin administration. Moreover, cardamonin blocked the nuclear translocation of NF-κB p65, inhibited NF-κB-luciferase activity, and downregulated NF-κB target genes expression. The present study clearly demonstrates a beneficial effect of cardamonin on experimental inflammatory bowel disease via a mechanism associated with suppression of toll-like receptor 4 expression and inactivation of NF-κB and mitogen-activated protein kinase pathways. This study may give insight into the further evaluation of the therapeutic potential of cardamonin or its derivatives for human inflammatory bowel disease.

show abstract

“…Information on diet, lifestyle, weight, height, medical treatment, environmental exposures, and other socioeconomic factors was collected at enrollment using questionnaires and interviews as described in detail elsewhere (28,(35)(36)(37). In short, a food-frequency questionnaire (FFQ) assessed diet consumption in 12 categories of predefined responses, ranking from "never" to "eight times or more per day."…”

Section: Dietary and Lifestyle Questionnairementioning

confidence: 99%

Meat and fiber intake and interaction with pattern recognition receptors (TLR1, TLR2, TLR4, and TLR10) in relation to colorectal cancer in a Danish prospective, case-cohort study

Kopp

Vogel

Tjønneland

et al. 2018

The American Journal of Clinical Nutrition

Self Cite

View full text Add to dashboard Cite

Background: Meat and dietary fiber are associated with increased and decreased risk of colorectal cancer (CRC), respectively. Toll-like receptors (TLRs) regulate the intestinal immune response in a complex interplay between the mucosal epithelium and the microbiota and may therefore be important modulators of diet-induced CRC together with other inflammatory mediators. Objective: Our aim was to investigate the association between functional TLR polymorphisms and risk of CRC and the interaction with dietary factors. Additionally, interactions with previously studied polymorphisms in IL10, IL1B, PTGS2, and NFKB1 were assessed in order to examine possible biological pathways in meat-induced CRC. Design: A nested case-cohort study of 897 CRC cases and 1689 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study encompassing 57,053 persons was performed using Cox proportional hazard models and the likelihood ratio test. Results: We found associations between polymorphisms in TLR2 (P = 0.018) and TLR4 (P = 0.044) and risk of CRC per se, interactions between intake of red and processed meat (10 g/d) and polymorphisms in TLR1 (P-interaction = 0.032) and TLR10 (P-interaction = 0.026 and 0.036), and intake of cereals (50 g/d) and TLR4 (P-interaction = 0.044) in relation to risk of CRC. Intake of red and processed meat also interacted with combinations of polymorphisms in TLR1 and TLR10 and polymorphisms in NFKB1, IL10, IL1B, and PTGS2 (P-interaction; TLR1/rs4833095 × PTGS2/rs20417 = 0.021, TLR10/rs11096955 × IL10/rs3024505 = 0.047, TLR10/rs11096955 × PTGS2/rs20417 = 0.017, TLR10/rs4129009 × NFKB1/rs28362491 = 0.027, TLR10/rs4129009 × IL1B/rs4848306 = 0.020, TLR10/rs4129009 × IL1B/rs1143623 = 0.021, TLR10/rs4129009 × PTGS2/rs20417 = 0.027), whereas intake of dietary fiber (10 g/d) interacted with combinations of polymorphisms in TLR4, IL10, and PTGS2 (P-interaction; TLR4/rs1554973 × IL10/rs3024505 = 0.0012, TLR4/rs1554973 × PTGS2/rs20417 = 0.0041, TLR4/rs1554973 × PTGS2/rs5275 = 0.0064). Conclusions: Our study suggests that meat intake may activate TLRs at the epithelial surface, leading to CRC via inflammation by nuclear transcription factor-κB-initiated transcription of inflammatory genes, whereas intake of fiber may protect against CRC via TLR4-mediated secretion of interleukin-10 and cyclooxygenase-2. Our results should be replicated in other prospective cohorts with well-characterized participants. The trial was registered at www.clinicaltrials.gov as NCT03250637.Am J Clin Nutr 2018;107:465-479.

show abstract

Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease

Abstract: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.

Cited by 80 publications

References 74 publications

Different Genetic Expression Profiles of Oxidative Stress and Apoptosis-Related Genes in Crohn’s Disease

Different Genetic Expression Profiles of Oxidative Stress and Apoptosis-Related Genes in Crohn’s Disease

The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis

Meat and fiber intake and interaction with pattern recognition receptors (TLR1, TLR2, TLR4, and TLR10) in relation to colorectal cancer in a Danish prospective, case-cohort study

Contact Info

Product

Resources

About