Acute colitis chronically alters immune infiltration mechanisms and sensory neuro-immune interactions

Campaniello, Melissa A.; Mavrangelos, Chris; Eade, Samuel; Harrington, Andrea M.; Blackshaw, L. Ashley; Brierley, Stuart M.; Smid, Scott D.; Hughes, Patrick A.

doi:10.1016/j.bbi.2016.11.015

Cited by 18 publications

(40 citation statements)

References 47 publications

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“…Myeloperoxidase activity in the distal colon was determined as previously described (15,16). Briefly, phosphate-buffered saline-washed tissue segments were homogenized in 0.5% hexadecyl-trimethylammonium bromide (Sigma-Aldrich) and reacted with o-dianisidine hydrochloride (Sigma-Aldrich).…”

Section: Myeloperoxidase Activitymentioning

confidence: 99%

“…Proteins were extracted from the distal colon as previously described (14,15). Briefly, colon segments were homogenized for 5 min in cell extraction buffer (ThermoFisher Scientific) supplemented with protease inhibitor cocktail (Sigma-Aldrich), 1 mM phenyl-methanesulfonyl fluoride (Sigma-Aldrich), and 50 mM ethylenediaminetetraacetic acid at 1 mL/50 mg of tissue.…”

Section: Il-1β Elisamentioning

confidence: 99%

“…Supernatant was collected and stored at 280°C until analysis. IL-1b concentrations were determined by OptEIA IL-1b ELISA (BD Biosciences) as previously described (14,15). The limit of sensitivity was less than 4 pg/mL.…”

Section: Il-1β Elisamentioning

confidence: 99%

“…The limit of sensitivity was less than 4 pg/mL. Concentrations were normalized to total protein concentration as determined by a bicinchoninic acid assay (Abcam) as previously described (15).…”

Section: Il-1β Elisamentioning

confidence: 99%

“…Colon lamina propria mononuclear cells (LPMCs) were isolated enzymatically, essentially as previously described (14,15). Briefly, the colon was excised free of fat and blood vessels, flushed with cold phosphate-buffered saline, roughly chopped, and incubated in 4-(2hydroxyethyl)-1-piperazineethanesulfonic acid buffered Hanks balanced salt solution supplemented with 1 mM ethylenediaminetetraacetic and 1 mM dithiothreitol (20 min, 37°C, gentle shaking).…”

Section: Flow Cytometrymentioning

confidence: 99%

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Immuno-PET of Innate Immune Markers CD11b and IL-1β Detects Inflammation in Murine Colitis

et al. 2018

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Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. The diagnosis and monitoring of IBD are reliant on endoscopy, which is invasive and does not provide information on specific mediators. Symptom flare in IBD is associated with increased activation of innate immune pathways. Immuno-PET approaches have previously demonstrated the ability to detect colitis; however, a direct comparison of antibodies targeted to innate immune mediators and cells has not been done. We aimed to compare immuno-PET of antibodies to IL-1β and CD11b against standard 18 F-FDG and MRI approaches to detect colonic inflammation. Methods: Colonic concentrations of IL-1β and myeloperoxidase were determined by ELISA, and colonic infiltration by CD11b-positive CD3-negative innate immune cells was determined by flow cytometry and compared between healthy and dextran sodium sulphate-treated colitic mice. PET of 89 Zr-lα-IL-1β, 89 Zr-α-CD11b, and 18 F-FDG was compared by volume-of-interest analysis and with MRI by region-of-interest analysis. Imaging results were confirmed by ex vivo biodistribution analysis. Results: Colonic inflammation was associated with impaired colonic epithelial barrier permeability, increased colonic IL-1β and myeloperoxidase concentrations, and increased CD11b-positive CD3-negative innate immune cell infiltration into the colon. 89 Zr-α-IL-1β and 89 Zr-α-CD11b immuno-PET detected colonic inflammation, as did 18 F-FDG, and all PET tracers were more sensitive than MRI. Although 18 F-FDG volumes of interest correlated with colitis severity and a strong trend was observed with 89 Zr-α-IL-1β, no correlation was observed for 89 Zr-α-CD11b or MRI. 89 Zr-α-IL-1β was distributed mainly to the gastrointestinal tract, whereas 89 Zr-α-CD11b was distributed to more tissue types. Conclusion: Immuno-PET using antibodies directed to innate immune markers detected colonic inflammation, with 89 Zr-α-IL-1β providing a more tissue-specific signal than 89 Zr-α-CD11b. Development of these technologies for human subjects will potentially provide a less invasive approach than endoscopy for diagnosing and monitoring IBD. Detects Inflammation inβ Immuno-PET of Innate Immune Markers CD11b and IL-1 http://jnm.snmjournals.org/content/60/6/858 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

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Section: Myeloperoxidase Activitymentioning

confidence: 99%

Section: Il-1β Elisamentioning

confidence: 99%

Section: Il-1β Elisamentioning

confidence: 99%

Section: Il-1β Elisamentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

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Immuno-PET of Innate Immune Markers CD11b and IL-1β Detects Inflammation in Murine Colitis

et al. 2018

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Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis

Costello

Hughes

Waters

et al. 2019

JAMA

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IMPORTANCE High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity. OBJECTIVE To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool. DESIGN, SETTING, AND PARTICIPANTS A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017. INTERVENTIONS Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months. MAIN OUTCOMES AND MEASURES The primary outcome was steroid-free remission of UC, defined as a total Mayo score of Յ2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events. RESULTS Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group. CONCLUSIONS AND RELEVANCE In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.

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Empagliflozin attenuates intestinal inflammation through suppression of nitric oxide synthesis and myeloperoxidase activity in in vitro and in vivo models of colitis

et al. 2023

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Inflammatory bowel diseases (IBD) are characterized by chronic and relapsing inflammation affecting the gastrointestinal (GI) tract. The incidence and prevalence of IBD are relatively high and still increasing. Additionally, current therapeutic strategies for IBD are not optimal. These facts urge todays’ medicine to find a novel way to treat IBD. Here, we focused on the group of anti-diabetic drugs called gliflozins, which inhibit sodium glucose co-transporter type 2 (SGLT-2). Numerous studies demonstrated that gliflozins exhibit pleiotropic effect, including anti-inflammatory properties. In this study, we tested the effect of three gliflozins; empagliflozin (EMPA), dapagliflozin (DAPA), and canagliflozin (CANA) in in vitro and in vivo models of intestinal inflammation. Our in vitro experiments revealed that EMPA and DAPA suppress the production of nitric oxide in LPS-treated murine RAW264.7 macrophages. In in vivo part of our study, we showed that EMPA alleviates acute DSS-induced colitis in mice. Treatment with EMPA reduced macro- and microscopic colonic damage, as well as partially prevented from decrease in tight junction gene expression. Moreover, EMPA attenuated biochemical inflammatory parameters including reduced activity of myeloperoxidase. We showed that SGLT-2 inhibitors act as anti-inflammatory agents independently from their hypoglycemic effects. Our observations suggest that gliflozins alleviate inflammation through their potent effects on innate immune cells.

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Acute colitis chronically alters immune infiltration mechanisms and sensory neuro-immune interactions

Cited by 18 publications

References 47 publications

Immuno-PET of Innate Immune Markers CD11b and IL-1β Detects Inflammation in Murine Colitis

Immuno-PET of Innate Immune Markers CD11b and IL-1β Detects Inflammation in Murine Colitis

Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis

Empagliflozin attenuates intestinal inflammation through suppression of nitric oxide synthesis and myeloperoxidase activity in in vitro and in vivo models of colitis

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