Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires, Klára; Tóth, Éva Viktória; Zádori, Zoltán

doi:10.2174/13816128113199990417

Cited by 40 publications

(32 citation statements)

References 328 publications

(370 reference statements)

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“…In the rest regions (f, c and g, inflammation related), for gut advantage transcripts, in region f, IFN-γ and IFN induced proteins implied Th1 response46; and the immunoglobulin heavy chain (μ and another one) transcripts suggested coexistence of IgM and probably IgT4748. In region c, proinflammatory factors (IL-1β and CCR6) and T cell markers (CD3 and CD8) indicated CTL responses occurred in the inflammatory gut49; and F-type lectin was in line with other reports of fish inflammation5051.…”

Section: Discussionmentioning

confidence: 99%

Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies

Song

Wang

et al. 2016

Sci Rep

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The gut-associated lymphoid tissue, connected with liver via bile and blood, constructs a local immune environment of both defense and tolerance. The gut-liver immunity has been well-studied in mammals, yet in fish remains largely unknown, even though enteritis as well as liver and gallbladder syndrome emerged as a limitation in aquaculture. In this study, we performed integrative bioinformatic analysis for both transcriptomic (gut and liver) and proteomic (intestinal mucus and bile) data, in both healthy and infected tilapias. We found more categories of immune transcripts in gut than liver, as well as more adaptive immune in gut meanwhile more innate in liver. Interestingly reduced differential immune transcripts between gut and liver upon inflammation were also revealed. In addition, more immune proteins in bile than intestinal mucus were identified. And bile probably providing immune effectors to intestinal mucus upon inflammation was deduced. Specifically, many key immune transcripts in gut or liver as well as key immune proteins in mucus or bile were demonstrated. Accordingly, we proposed a hypothesized profile of fish gut-liver immunity, during either homeostasis or inflammation. Current data suggested that fish gut and liver may collaborate immunologically while keep homeostasis using own strategies, including potential unique mechanisms.

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Section: Discussionmentioning

confidence: 99%

Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies

Song

Wang

et al. 2016

Sci Rep

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“…Their pathogenesis is complex, involving various predisposing environmental and genetic factors, which together with the altered intestinal flora can induce mucosal disruption and result in penetration of luminal antigens into the gut wall, followed by an ungoverned immune response and a chronic inflammatory reaction (Xavier and Podolsky, 2007;Gyires et al, 2014;Neurath, 2014). Numerous agents are available to treat IBD patients (Bryant et al, 2015), but many of them cause severe adverse reactions, or fail to maintain long-term remission, and a lot of effort is currently put into finding new therapeutic approaches (Gyires et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of 2A-Adrenoceptors Ameliorates Dextran Sulfate Sodium-Induced Acute Intestinal Inflammation in Mice

Zádori

Tóth

Fehér

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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It has been hypothesized that a 2 -adrenoceptors (a 2 -ARs) may be involved in the pathomechanism of colitis; however, the results are conflicting because both aggravation and amelioration of colonic inflammation have been described in response to a 2 -AR agonists.Therefore, we aimed to analyze the role of a 2 -ARs in acute murine colitis. The experiments were carried out in wild-type, a 2A -, a 2B -, and a 2C -AR knockout (KO) C57BL/6 mice. Colitis was induced by dextran sulfate sodium (DSS, 2%); alpha 2 -AR ligands were injected i.p. The severity of colitis was determined both macroscopically and histologically. Colonic myeloperoxidase (MPO) and cytokine levels were measured by enzyme-linked immunosorbent assay and proteome profiler array, respectively. The nonselective a 2 -AR agonist clonidine induced a modest aggravation of DSSinduced colitis. It accelerated the disease development and markedly enhanced the weight loss of animals, but did not influence the colon shortening, tissue MPO levels, or histologic score. Clonidine induced similar changes in a 2B -and a 2C -AR KO mice, whereas it failed to affect the disease activity index scores and caused only minor weight loss in a 2A -AR KO animals. In contrast, selective inhibition of a 2A -ARs by BRL 44408 significantly delayed the development of colitis; reduced the colonic levels of MPO and chemokine (C-C motif) ligand 3, chemokine (C-X-C motif) ligand 2 (CXCL2), CXCL13, and granulocytecolony stimulating factor; and elevated that of tissue inhibitor of metalloproteinases-1. In this work, we report that activation of a 2 -ARs aggravates murine colitis, an effect mediated by the a 2A -AR subtype, and selective inhibition of these receptors reduces the severity of gut inflammation.

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“…Numerous studies have shown that the Toll-like receptor-4 (TLR4) pathway is a major downstream signalling pathway for LPS. Notably, TLR4 is not only associated with microbial pathogenesis but also with multiple diseases such as IBD, autoimmune and allergic diseases [23-25]. Moreover, TLR4 is involved in the inflammation response, particularly in the secretion of inflammatory cytokines because it links several key inflammation-associated pathways such as NF-κB, MAPK and IRF3 [25-27].…”

Section: Resultsmentioning

confidence: 99%

“…Notably, TLR4 is not only associated with microbial pathogenesis but also with multiple diseases such as IBD, autoimmune and allergic diseases [23-25]. Moreover, TLR4 is involved in the inflammation response, particularly in the secretion of inflammatory cytokines because it links several key inflammation-associated pathways such as NF-κB, MAPK and IRF3 [25-27]. As MIMP showed a significant inhibitory effect on LPS-induced inflammation, we hypothesized that MIMP may regulate inflammatory cytokines through affecting the TLR4 pathway.…”

Section: Resultsmentioning

confidence: 99%

Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines

Yin¹,

Yan

Weng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recent studies have demonstrated that the manipulation of the gut microbiome represents a promising treatment for inflammatory bowel disease (IBD). We previously identified micro integral membrane protein (MIMP) as the smallest domain of surface layer protein from Lactobacillus Plantarum. However, the therapeutic relevance of MIMP in IBD remains unknown. Methods: We initially employed a dextran sodium sulphate (DSS)-induced colitis model and evaluated the effect of MIMP on the inflammation response, intestinal barrier and gut microbiota using histological examination, Fluorescein isothiocyanate-Dextran detection and pyrosequencing analysis respectively. We then established peripheral blood mononuclear cells (PBMCs) and an epithelial CaCO-2 co-culture model to investigate the regulatory role of MIMP in inflammatory cytokines. The level changes of inflammatory cytokines were detected using Enzyme-linked immunosorbent and real-time polymerase chain reaction assay. The involved regulatory mechanisms were investigated mainly using dual luciferase reporter and chromatin immunoprecipitation assay. Results: In the DSS-induced colitis model, we observed that MIMP intervention effectively improved the body weight loss, increased the colon length and decreased disease activity index. Consistently, the inflammation scores in the MIMP treatment group were significantly lower than those in the DSS treatment group. Furthermore, MIMP intervention was found to successfully neutralize DSS treatment by decreasing the expression of pro-inflammatory cytokines (IFN-γ, IL-17 and IL-23) and increasing the expression of anti-inflammatory cytokines (IL-4 and IL-10). Notably, the permeability assay demonstrated that the MIMP treatment group was remarkably lower than that in the DSS treatment group. We also showed that MIMP improved gut microbiota dysbiosis caused by DSS-induced inflammation. Additionally, in PBMCs and the CaCO-2 co-culture model, MIMP showed an obvious suppressive effect on lipopolysaccharide-induced inflammation in a time- and dose-dependent manner. Furthermore, we revealed that MIMP could modulate inflammatory cytokine expression through the toll-like receptor 4 pathway and histone acetylation. Conclusions: Our results suggested that MIMP showed a significant anti-inflammatory effect through regulating the gut barrier, microbiota and inflammatory cytokines. MIMP may have translational relevance as clinically relevant therapy for IBD patients.

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Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Cited by 40 publications

References 328 publications

Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies

Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies

Inhibition of 2A-Adrenoceptors Ameliorates Dextran Sulfate Sodium-Induced Acute Intestinal Inflammation in Mice

Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines

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