Nod-Like Receptor Pyrin-Containing Protein 6 (NLRP6) Is Up-regulated in Ileal Crohn’s Disease and Differentially Expressed in Goblet Cells

Ranson, Nicole; Veldhuis, Mark; Mitchell, B.; Fanning, Scott B.; Cook, Anthony; Kunde, Dale; Eri, Rajaraman

doi:10.1016/j.jcmgh.2018.03.001

Cited by 18 publications

(24 citation statements)

References 13 publications

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“…NLRs are composed of 23 family members in the human genome and 34 in the mouse genome . In recent years, Ranson et al observed that the inflammasome component NLRP6 is up‐regulated in human ileal Crohn's disease(CD), but not to a significant extent in human ulcerative colitis. In contrast, Misagh Alipour et al found a trend for reduced NLRP6 expression in IBD subsets but this did not reach statistical significance.…”

Section: Introductionmentioning

confidence: 99%

The protective roles of NLRP6 in intestinal epithelial cells

et al. 2018

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The evolution of chronic inflammatory diseases is thought to be due to a combination of host genetic variations and environmental factors that include the alteration of intestinal flora, termed “dysbiosis.” The intestinal mucosal barrier includes a chemical barrier and physical barrier that have important roles in protecting the intestine against inflammatory injury. The chemical barrier includes antimicrobial peptides ( AMP s), and the physical barrier includes a mucous layer, a monolayer of intestinal epithelial cells and cell junctions. The intestinal mucosal barrier is not a static barrier, but rather, it strongly interacts with the gut microbiome and cells of the immune system. Correct expression of AMP s, together with mucus and balanced epithelial cell proliferation, prevents the occurrence of disease. NLRP 6, a member of the nucleotide‐binding domain, leucine‐rich repeat‐containing ( NLR ) innate immune receptor family, participates in the progression of intestinal inflammation and enteric pathogen infections. It has become apparent in recent years that NLRP 6 is important in disease pathogenesis, as it responds to internal ligands that lead to the release of AMP s and mucus, thus regulating the regeneration of intestinal epithelial cells. This review summarizes the activation of NLRP 6 and its protective role in the intestinal epithelial cell.

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Section: Introductionmentioning

confidence: 99%

The protective roles of NLRP6 in intestinal epithelial cells

et al. 2018

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“…Most studies to date have assigned a protective role to the activation of NLRP6 in various intestinal pathologies, with both intestinal inflammation and tumorigenesis significantly aggravated in the absence of NLRP6 [ 58 ]. However, a recent line of research has described that NLRP6 is upregulated in ileal Crohn’s disease, and a pathogenic role for NLRP6 in alloimmune-mediated intestinal damage has been proposed [ 59 ]. It seems that the regulation of NLRP6 expression/function depends on the biological context (e.g., under normal homeostatic vs during pathologic chronic inflammation) or even section of the GI tract studied [ 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, a recent line of research has described that NLRP6 is upregulated in ileal Crohn’s disease, and a pathogenic role for NLRP6 in alloimmune-mediated intestinal damage has been proposed [ 59 ]. It seems that the regulation of NLRP6 expression/function depends on the biological context (e.g., under normal homeostatic vs during pathologic chronic inflammation) or even section of the GI tract studied [ 59 , 60 ]. Future investigations are required to fully understand these differences.…”

Section: Discussionmentioning

confidence: 99%

Oleanolic acid ameliorates intestinal alterations associated with EAE

Gutiérrez

Gallardo

Ruíz

et al. 2020

J Neuroinflammation

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Background Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment. Methods Mice with MOG35–55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects. Results We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract. Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS. Conclusion These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.

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“…84 By acting through specific GPCRs, SCFAs potentially activate NLRP6 to facilitate intestinal goblet cells to secrete Mucin2. [85][86][87] Clostridia-derived butyrate alleviates GvHD by potentiating IEC proliferation and apical junctional protein expression through HDAC inhibition. 88 Butyrate elicits anti-inflammatory IL-10 receptor-α subunit by activating STAT3 and inhibiting HDAC, which increases the production of colonic Mucin2 and tight junction proteins and consequently protects against LPS leakage and inflammation.…”

Section: Scfas Confer Colonization Resistance Against Intestinal Pathmentioning

confidence: 99%

Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome

Zhang

Tang

Chen

et al. 2019

Sig Transduct Target Ther

184

151

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The trillions of microorganisms in the gut microbiome have attracted much attention recently owing to their sophisticated and widespread impacts on numerous aspects of host pathophysiology. Remarkable progress in large-scale sequencing and mass spectrometry has increased our understanding of the influence of the microbiome and/or its metabolites on the onset and progression of extraintestinal cancers and the efficacy of cancer immunotherapy. Given the plasticity in microbial composition and function, microbial-based therapeutic interventions, including dietary modulation, prebiotics, and probiotics, as well as fecal microbial transplantation, potentially permit the development of novel strategies for cancer therapy to improve clinical outcomes. Herein, we summarize the latest evidence on the involvement of the gut microbiome in host immunity and metabolism, the effects of the microbiome on extraintestinal cancers and the immune response, and strategies to modulate the gut microbiome, and we discuss ongoing studies and future areas of research that deserve focused research efforts.

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Nod-Like Receptor Pyrin-Containing Protein 6 (NLRP6) Is Up-regulated in Ileal Crohn’s Disease and Differentially Expressed in Goblet Cells

Cited by 18 publications

References 13 publications

The protective roles of NLRP6 in intestinal epithelial cells

The protective roles of NLRP6 in intestinal epithelial cells

Oleanolic acid ameliorates intestinal alterations associated with EAE

Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome

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