Toward Point-of-Care Diagnostics to Monitor MMP-9 and TNF-α Levels in Inflammatory Bowel Disease

Liu, Dandan; Viennois, Émilie; Fang, Jieqiong; Merlin, Didier; Iyer, Suri S.

doi:10.1021/acsomega.0c05115

Cited by 14 publications

(6 citation statements)

References 30 publications

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“…Notably, we found that TNF-α, but not IFN‐γ induced significant upregulation of MMP-9, MMP-10 and MMP-13 whereas both cytokines were able to upregulate MMP-1. A correlation between TNF-α and MMP-9 has been outlined in IBD, but as of yet no causal link has been identified ( 74 ). Furthermore, TNF-α significantly increased MMP-3 in inflamed IBD models.…”

Section: Discussionmentioning

confidence: 99%

An in vitro model to study immune activation, epithelial disruption and stromal remodelling in inflammatory bowel disease and fistulising Crohn’s disease

Mobbs,

Darling,

Przyborski

2024

Front. Immunol.

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At present, preclinical models of inflammatory bowel disease (IBD) are insufficient, limiting translation between research and new therapeutics. This is especially true for fistulising Crohn’s disease (CD), as the severe lack of relevant models hinders research progression. To address this, we present in vitro human IBD mucosal models that recapitulate multiple pathological hallmarks of IBD simultaneously in one model system - immune cell infiltration, stromal remodelling and epithelial disruption. Stimulation of models induces epithelial aberrations common in IBD tissue including altered morphology, microvilli abnormalities, claudin gene expression changes and increased permeability. Inflammatory biomarkers are also significantly increased including cytokines and chemokines integral to IBD pathogenesis. Evidence of extracellular matrix remodelling, including upregulated matrix-metalloproteinases and altered basement membrane components, suggests the models simulate pathological stromal remodelling events that closely resemble fistulising CD. Importantly, MMP-9 is the most abundant MMP and mimics the unique localisation observed in IBD tissue. The inflamed models were subsequently used to elucidate the involvement of TNF-α and IFN- γ in intestinal stromal remodelling, in which TNF-α but not IFN- γ induced MMP upregulation, specifically of MMP-3 and MMP-9. Collectively, our results demonstrate the potential of the IBD models for use in preclinical research in IBD, particularly for fistulising CD.

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Section: Discussionmentioning

confidence: 99%

An in vitro model to study immune activation, epithelial disruption and stromal remodelling in inflammatory bowel disease and fistulising Crohn’s disease

Mobbs,

Darling,

Przyborski

2024

Front. Immunol.

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“…Mast cells, which are orchestrated at the inflamed site, contain histamine and regulate the innate immunity, and they are responsible for the release of histamine and various inflammatory cytokines like IL-1β and TNF-α. These mediators are directly correlated with various inflammatory diseases including UC where they potentially mark for initiation and progression of diseases. − Moreover, pro-inflammatory cytokines like TNF-α, IL-13, IL-33, etc. play a crucial role in the progress of diseases, whereas anti-inflammatory cytokines like IL-10, IL-33, etc.…”

Section: Resultsmentioning

confidence: 99%

Thiol-Functionalized Cellulose-Grafted Copper Oxide Nanoparticles for the Therapy of Experimental Colitis in Swiss Albino Mice

Mishra¹,

Selim²,

Gowri³

et al. 2022

ACS Biomater. Sci. Eng.

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Ulcerative colitis (UC) is a chronic inflammatory disease, which deleteriously affects the lower end of the gastrointestinal tract, i.e., the colon and the rectum. UC affects colonic inflammatory homeostasis and disrupts intestinal barrier functions. Intestinal tissue damage activates the immune system and collectively worsens the disease condition via the production of various cytokines. Ongoing therapeutics of UC have marked limitations like rapid clearance, extensive first-pass metabolism, poor drug absorption, very low solubility, bioavailability, etc. Because of these restrictions, the management of UC demands a rational approach that selectively delivers the drug at the site of action to overcome the therapeutic limiting factors. Metallic nanoparticles (NPs) have good therapeutic efficacy against colitis, but their uses are limited due to adverse effects on the biological system. In this study, we have used biocompatible thiol-functionalized cellulose-grafted copper oxide nanoparticles (C-CuI/IIO NPs) to treat UC. The metal NPs alleviated the colitis condition as evidenced by the colon length and observed physical parameters. Analysis of histopathology demonstrated the recovery of the colon architecture damaged by dextran sulfate sodium-induced colitis. Treatment with C-CuI/IIO NPs reduced the disintegration of goblet cells and the retainment of sulfomucin. Significant downregulation of inflammatory markers like MPO activity, as well as levels of nitrite and TNF-α, was found following C-CuI/IIO NP treatment. The observations from the study suggested that intrarectal treatment of colitis with cellulose-based C-CuI/IIO NPs successfully combated the intestinal inflammatory condition.

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“…Liu et al. studied MMP-9 in excreta using nanoparticles ( 42 ). A study reported that TLR5 plays a key role in the inflammatory response in the intestine through animal tests on TLR5 and that disruption of TLR5 signaling triggers the TNFR2 signaling pathway, which leads to an inflammatory response in the intestine ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

The role of intestinal immune cells and matrix metalloproteinases in inflammatory bowel disease

et al. 2023

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Inflammatory bowel disease (IBD) has become globally intractable. MMPs play a key role in many inflammatory diseases. However, little is known about the role of MMPs in IBD. In this study, IBD expression profiles were screened from public Gene Expression Omnibus datasets. Functional enrichment analysis revealed that IBD-related specific functions were associated with immune pathways. Five MMPS-related disease markers, namely MMP-9, CD160, PTGDS, SLC26A8, and TLR5, were selected by machine learning and the correlation between each marker and immune cells was evaluated. We then induced colitis in C57 mice using sodium dextran sulfate and validated model construction through HE staining of the mouse colon. WB and immunofluorescence experiments confirmed that the expression levels of MMP-9, PTGDS, SLC26A8, and CD160 in colitis were significantly increased, whereas that of TLR5 were decreased. Flow cytometry analysis revealed that MMPs regulate intestinal inflammation and immunity mainly through CD8 in colitis. Our findings reveal that MMPs play a crucial role in the pathogenesis of IBD and are related to the infiltration of immune cells, suggesting that MMPs may promote the development of IBD by activating immune infiltration and the immune response. This study provides insights for further studies on the occurrence and development of IBD.

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Toward Point-of-Care Diagnostics to Monitor MMP-9 and TNF-α Levels in Inflammatory Bowel Disease

Cited by 14 publications

References 30 publications

An in vitro model to study immune activation, epithelial disruption and stromal remodelling in inflammatory bowel disease and fistulising Crohn’s disease

An in vitro model to study immune activation, epithelial disruption and stromal remodelling in inflammatory bowel disease and fistulising Crohn’s disease

Thiol-Functionalized Cellulose-Grafted Copper Oxide Nanoparticles for the Therapy of Experimental Colitis in Swiss Albino Mice

The role of intestinal immune cells and matrix metalloproteinases in inflammatory bowel disease

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