Targeting eotaxin‐1 and <scp>CCR</scp>3 receptor alleviates enteric neuropathy and colonic dysfunction in <scp>TNBS</scp>‐induced colitis in guinea pigs

Filippone, Rhiannon T; Robinson, Ainsley M; Jovanovska, Valentina; Stavely, Rhian; Apostolopoulos, Vasso; Bornstein, Joel C.; Nurgali, Kulmira

doi:10.1111/nmo.13391

Cited by 12 publications

(13 citation statements)

References 71 publications

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“…Their lifetime in tissues is variable, with a half-life of <1 d in blood and lung and ∼6 d in the small intestine ( Carlens et al, 2009 ). Parasitic infections and allergic or chronic inflammatory diseases lead to increased eosinophil infiltration, and eosinophils contribute to disease pathology ( Busse and Sedgwick, 1992 ; Filippone et al, 2018 ; Furuta et al, 2005 ; Mehta and Furuta, 2015 ; Smyth et al, 2013 ; Yantiss, 2015 ). Nevertheless, eosinophils may also regulate inflammation ( Masterson et al, 2015 ), and their functional potential is wide-ranging.…”

Section: Introductionmentioning

confidence: 99%

The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

Diny

Schonfeldova

Shapiro

et al. 2022

Journal of Experimental Medicine

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Eosinophils are potent sources of inflammatory and toxic mediators, yet they reside in large numbers in the healthy intestine without causing tissue damage. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response, cell–cell communication, extracellular matrix remodeling, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis. Eosinophils from AHR-deficient mice failed to fully express the intestinal gene expression program, including extracellular matrix organization and cell junction pathways. AHR-deficient eosinophils were functionally impaired in the adhesion to and degradation of extracellular matrix, were more prone to degranulation, and had an extended life span. Lack of AHR in eosinophils had wider effects on the intestinal immune system, affecting the T cell compartment in nave and helminth-infected mice. Our study demonstrates that the response to environmental triggers via AHR partially shapes tissue adaptation of eosinophils in the small intestine.

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Section: Introductionmentioning

confidence: 99%

The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

Diny

Schonfeldova

Shapiro

et al. 2022

Journal of Experimental Medicine

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“…mostly use traditional mammalian models. Conventional mammalian enteritis models are chemical-induced, for example, DSS (3,6-Disinapoylsucrose) was used to induce mice colitis [ 31 ], and TNBS (2,4,6-trinitro-Benzenesulfonic acid) was applied to induce guinea pig colitis [ 32 ]. It is necessary to fast for 24–36 hrs before chemical drug induction to allow the animals to empty their feces, this is not consistent with the intestinal environment of patients with enteritis and cannot completely simulate the patient’s conditions.…”

Section: Introductionmentioning

confidence: 99%

Bifidobacterium lactis BL-99 modulates intestinal inflammation and functions in zebrafish models

Chen

Liu

Dai³

et al. 2022

PLoS ONE

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This study was designed to explore the therapeutics and the mechanisms of a patented and marked gastric acid and intestine juice-resistant probiotics Bifidobacterium lactis BL-99 (B. lactis BL-99) on the intestinal inflammation and functions in the zebrafish models. After feeding for 6 hours, B. lactis BL-99 was fully retained in the larval zebrafish intestinal tract and stayed for over 24 hours. B. lactis BL-99 promoted the intestinal motility and effectively alleviated aluminum sulfate-induced larval zebrafish constipation (p < 0.01). Irregular high glucose diet induced adult zebrafish intestinal functional and metabolic disorders. After fed with B. lactis BL-99, IL-1β gene expression was significantly down-regulated, and IL-10 and IL-12 gene levels were markedly up-regulated in this model (p < 0.05). The intestinal lipase activity was elevated in the adult zebrafish intestinal functional disorder model after B. lactis BL-99 treatment (p < 0.05), but tryptase content had no statistical changes (p > 0.05). B. lactis BL-99 improved the histopathology of the adult zebrafish intestinal inflammation, increased the goblet cell numbers, and up-and-down metabolites were markedly recovered after treatment of B. lactis BL-99 (p < 0.05). These results suggest that B. lactis BL-99 could relieve intestinal inflammation and promote intestinal functions, at least in part, through modulating intestinal and microbial metabolism to maintain intestinal health.

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“…Eosinophil accumulation in the inflamed intestines coincides with chronic intestinal inflammation, disease severity, and impediments to gastrointestinal (GI) functions during colitis [ 10 , 11 ]. It has been postulated that eosinophils can interact with nerve fibers innervating the GI tract, as previously observed in patients with IBD and acute models of colitis [ 12 , 13 ]. In the intestinal mucosa, eosinophils are functionally required to regulate intestinal integrity and provide provisional immunity against antigen invasion.…”

Section: Introductionmentioning

confidence: 96%

“…It has been postulated that eosinophil activity in the inflamed intestine results in clinical symptoms and GI dysfunction [ 55 , 56 , 57 , 58 ]. Thus, therapies targeting eosinophil infiltration and activation have been considered [ 13 , 59 , 60 , 61 ].…”

Section: Introductionmentioning

confidence: 99%

“…Targeting eosinophil accumulation via CCR3-evoked chemotaxis has been proposed as a viable candidate for alleviating damage to the inflamed GI tract [ 1 , 7 , 13 , 62 ]. In the inflamed intestines from patients with IBD and corresponding animal models of colitis, persistent accumulation of eosinophils localizing with nerve fibers has been observed, resulting in altered GI functions [ 12 , 13 , 63 , 64 ].…”

Section: Introductionmentioning

confidence: 99%

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Potent CCR3 Receptor Antagonist, SB328437, Suppresses Colonic Eosinophil Chemotaxis and Inflammation in the Winnie Murine Model of Spontaneous Chronic Colitis

Filippone

Dargahi

Eri

et al. 2022

IJMS

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Eosinophils and their regulatory molecules have been associated with chronic intestinal inflammation and gastrointestinal dysfunctions; eosinophil accumulation in the gut is prominent in inflammatory bowel disease (IBD). The chemokine receptor CCR3 plays a pivotal role in local and systemic recruitment and activation of eosinophils. In this study, we targeted CCR3-ligand interactions with a potent CCR3 receptor antagonist, SB328437, to alleviate eosinophil-associated immunological responses in the Winnie model of spontaneous chronic colitis. Winnie and C57BL/6 mice were treated with SB328437 or vehicle. Clinical and histopathological parameters of chronic colitis were assessed. Flow cytometry was performed to discern changes in colonic, splenic, circulatory, and bone marrow-derived leukocytes. Changes to the serum levels of eosinophil-associated chemokines and cytokines were measured using BioPlex. Inhibition of CCR3 receptors with SB328437 attenuated disease activity and gross morphological damage to the inflamed intestines and reduced eosinophils and their regulatory molecules in the inflamed colon and circulation. SB328437 had no effect on eosinophils and their progenitor cells in the spleen and bone marrow. This study demonstrates that targeting eosinophils via the CCR3 axis has anti-inflammatory effects in the inflamed intestine, and also contributes to understanding the role of eosinophils as potential end-point targets for IBD treatment.

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Targeting eotaxin‐1 and CCR3 receptor alleviates enteric neuropathy and colonic dysfunction in TNBS‐induced colitis in guinea pigs

Abstract: This is the first study demonstrating that inhibition of CCR3-eotaxin axis alleviates enteric neuropathy and restores functional changes in the gut associated with TNBS-induced colitis.

Cited by 12 publications

References 71 publications

The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

Bifidobacterium lactis BL-99 modulates intestinal inflammation and functions in zebrafish models

Potent CCR3 Receptor Antagonist, SB328437, Suppresses Colonic Eosinophil Chemotaxis and Inflammation in the Winnie Murine Model of Spontaneous Chronic Colitis

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