Calprotectin protects against experimental colonic inflammation in mice

Aranda, Carlos J.; Ocón, Borja; Arredondo-Amador, María; Suárez, Marı́a Dolores; Zarzuelo, Antonio; Chazin, Walter J.; Medina, Fermín Sánchez de

doi:10.1111/bph.14449

Cited by 20 publications

(13 citation statements)

References 54 publications

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“…Moreover, MMI-0100 suppressed activation of CD11b+ and F4/80 positive cell induced by DSS, and dramatically decreased the expression level of a series of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, TGF- β, IFN-γ, IL-17A, COX-2 and iNOS. Previous articles have reported protective roles of calprotectin and lipocalin 2 against colitis [27,28]. Our data indicated that MMI-0100 significantly increased the expression level of calprotectin B and lipocalin 2, and down-regulated in the increase of CRP induced by DSS.…”

Section: Discussionsupporting

confidence: 66%

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

et al. 2019

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Backgrounds: This study aimed to investigate the protective effects of MMI-0100, a cell-penetrating peptide inhibitor of MAPK-activated protein kinase II (MK2), on acute colitis induced by dextran sodium sulfate (DSS). Mice were injected intraperitoneally with different doses of MMI-0100 (0.5 and 1 mg/kg per day, six days). The physiological indexes, the parameters for colonic pathological injury and the intensity of inflammatory responses were evaluated by histological staining, quantitative PCR, western blotting, and immunostaining. MMI-0100 attenuated DSS-induced body weight loss, colon length shortening, and colonic pathological injury, including decreased myeloperoxidase (MPO) and inhibited inflammatory cell infiltration. MMI-0100 suppressed DSS-induced activation of CD11b+ and F4/80 positive cell, and dramatically decreased the expression of a series of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, TGF- β, IFN-γ, IL-17A, COX-2 and iNOS. A TUNEL assay showed that MMI-0100 protected against DSS-induced apoptosis. This is consistent with the results of Western blotting assay in apoptosis-related proteins including Bcl-2, BAX, caspase-3. The anti-inflammatory effects of MMI-0100 on DSS-induced colitis were achieved by down-regulating the phosphorylation level of MK2, IκBα and p65 protein. The current study clearly demonstrates a protective role for MMI-0100 in experimental IBD.

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Section: Discussionsupporting

confidence: 66%

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

et al. 2019

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“…RAGE activity has already been linked to active IBD [15] as well as other inflammatory diseases including diabetes, Alzheimer’s, airway inflammation, cancer and haemorrhagic shock [16]. Additionally, several RAGE ligands have been identified as associated with the inflammation in IBD, including calprotectin, EN-RAGE and HMGB1 [17–19]. Thus, our data from the mouse model shows a clear link to known pathology in IBD.…”

Section: Discussionsupporting

confidence: 54%

Differential expression of soluble receptor for advanced glycation end-products (sRAGE) in mice susceptible or resistant to chronic colitis

Bramhall

Rich

Chakraborty

et al. 2019

Preprint

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23Aims: Identifying the factors that contribute to chronicity in inflamed colitic tissue is not 24 trivial. However, in mouse models of colitis, we can investigate at preclinical timepoints. We 25 sought to validate murine Trichuris muris infection as a model for identification of factors 26 that promote development of chronic colitis. 27 Methods:We compared preclinical changes in mice with a resolving immune response to T. 28 muris (resistant) versus mice that fail to expel the worms and develop chronic colitis 29 (susceptible). Findings were then validated in healthy controls and patients with suspected 30 or confirmed IBD. 31 Results: The Receptor for Advanced Glycation End Products (Rage) was highly dysregulated 32 between resistant and susceptible mice prior to the onset of any pathological signs. 33 Increased soluble RAGE (sRAGE) in the serum and faeces of resistant mice correlated with 34 reduced colitis scores. Mouse model findings were validated in a preliminary clinical study: 35 faecal sRAGE was differentially expressed in patients with active IBD compared with IBD in 36 remission, patients with IBD excluded or healthy controls. 37Conclusion: Pre-clinical changes in mouse models can identify early pathways in the 38 development of chronic inflammation that human studies cannot. We identified the decoy 39 receptor sRAGE as a potential mechanism for protection against chronic inflammation in 40 colitis in mice and humans. We propose that the RAGE pathway is clinically relevant in the 41 onset of chronic colitis, and that further study of sRAGE in IBD may provide a novel 42 diagnostic and therapeutic target. 43 44

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“…Fecal calprotectin changes were seen in our colitic mice fed differing iron diets, being greater in those animals consuming an iron-deficient diet in the acute colitis model, and with the iron supplemented diet in the chronic colitis model, most likely reflecting an enhanced protective response against inflammation-induced damage [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Iron Deficiency and Dietary Iron Excess Exacerbate Acute Dextran Sodium Sulphate-Induced Colitis and Are Associated with Significant Dysbiosis

Mahalhal

Burkitt

Duckworth

et al. 2021

IJMS

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Background: Oral iron supplementation causes gastrointestinal side effects. Short-term alterations in dietary iron exacerbate inflammation and alter the gut microbiota, in murine models of colitis. Patients typically take supplements for months. We investigated the impact of long-term changes in dietary iron on colitis and the microbiome in mice. Methods: We fed mice chow containing differing levels of iron, reflecting deficient (100 ppm), normal (200 ppm), and supplemented (400 ppm) intake for up to 9 weeks, both in absence and presence of dextran sodium sulphate (DSS)-induced chronic colitis. We also induced acute colitis in mice taking these diets for 8 weeks. Impact was assessed (i) clinically and histologically, and (ii) by sequencing the V4 region of 16S rRNA. Results: In mice with long-term changes, the iron-deficient diet was associated with greater weight loss and histological inflammation in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a change in the microbiome in DSS-treated mice consuming 100 ppm and 400 ppm iron diets, and control mice consuming the 400 ppm iron diet. Proteobacteria levels increased significantly, and Bacteroidetes levels decreased, in the 400 ppm iron DSS group at day-63 compared to baseline. Conclusions: Long-term dietary iron alterations affect gut microbiota signatures but do not exacerbate chronic colitis, however acute colitis is exacerbated by such dietary changes. More work is needed to understand the impact of iron supplementation on IBD. The change in the microbiome, in patients with colitis, may arise from the increased luminal iron and not simply from colitis.

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Calprotectin protects against experimental colonic inflammation in mice

Abstract: Calprotectin exerted protective effects in experimental colitis when given by the intrarectal route, by actions that appear to involve effects on the epithelium.

Cited by 20 publications

References 54 publications

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

Differential expression of soluble receptor for advanced glycation end-products (sRAGE) in mice susceptible or resistant to chronic colitis

Long-Term Iron Deficiency and Dietary Iron Excess Exacerbate Acute Dextran Sodium Sulphate-Induced Colitis and Are Associated with Significant Dysbiosis

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