Formyl Peptide Receptors and Annexin A1: Complementary Mechanisms to Infliximab in Murine Experimental Colitis and Crohn’s Disease

Non-responsiveness to anti-TNF-α therapies presents relevant rates in inflammatory bowel disease patients, presenting the need to find biomarkers involved in therapeutic efficacy. Herein, we demonstrate that higher levels of colonic formyl peptide receptor 1 and annexin A1 correlate with histological recovery in Crohn’s disease patients under remission. Using the dextran sulfate sodium colitis model in mice, we suggest that infliximab induces annexin A1 expression and secretion in activated intestinal leukocytes. Conversely, this mechanism might stimulate epithelial formyl peptide receptors, inducing wound healing and consequent histological remission. Our data indicate that assessing intestinal expressions of formyl peptide receptors and annexin A1 might provide precious information on the disease activity and responsiveness to infliximab in inflammatory bowel disease patients.

Download Full-text

Aspirin-triggered lipoxin enhances macrophage phagocytosis of bacteria while inhibiting inflammatory cytokine production

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00042.2011 ◽

2011 ◽

Vol 301 (3) ◽

pp. G487-G497 ◽

Cited By ~ 35

Author(s):

David Prescott ◽

Derek M. McKay

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Human Peripheral Blood ◽

Formyl Peptide Receptor ◽

Lipid Mediator ◽

Independent Manner ◽

Macrophage Phagocytosis ◽

Inflammatory Bowel

The macrophage plays a major role in the induction and resolution phases of inflammation; however, how lipid mediator-derived signals may modulate macrophage function in the resolution of inflammation driven by microbes (e.g., in inflammatory bowel disease) is not well understood. We examined the effects of aspirin-triggered lipoxin (ATL), a stable analog of lipoxin A4, on the antimicrobial responses of human peripheral blood mononuclear cell-derived macrophages and the monocytic THP-1 cell line. Additionally, we assessed the expression and localization of the lipoxin receptor, formyl peptide receptor 2 (FPR2), in colonic mucosal biopsies from patients with Crohn's disease to determine whether the capacity for lipoxin signaling is altered in inflammatory bowel disease. We found that THP-1 cells treated with ATL (100 nM) displayed increased phagocytosis of inert fluorescent beads and Escherichia coli in a scavenger receptor- and PI3K-dependent, opsonization-independent manner. This ATL-induced increase in phagocytosis was also observed in primary human macrophages, where it was associated with an inhibition of E. coli -induced IL-1β and IL-8 production. Finally, we found that FPR2 gene expression was increased approximately sixfold in the colon of patients with Crohn's disease, a finding reproduced in vitro by the treatment of THP-1 cells with interferon-γ or lipopolysaccharide. These results suggest that lipoxin signaling is upregulated in inflammatory environments, and, in addition to their known role in tissue resolution following injury, lipoxins can enhance macrophage clearance of invading microbes.

Download Full-text

Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

Nuklearmedizin ◽

10.1055/s-0038-1629438 ◽

1988 ◽

Vol 27 (03) ◽

pp. 83-86 ◽

Cited By ~ 3

Author(s):

B. Briele ◽

F. Wolf ◽

H. J. Biersack ◽

F. F. Knapp ◽

A. Hotze

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Cell Uptake ◽

Disease Extent ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

Download Full-text

CLINCAL EFFECTIVENESS OF GOLIMUMAB IN CROHN’S DISEASE – AN OBSERVATIONAL STUDY BASED ON THE SWEDISH NATIONAL QUALITY REGISTRY FOR INFLAMMATORY BOWEL DISEASE

10.26226/morressier.59a6b348d462b80290b54e3d ◽

2017 ◽

Author(s):

Sara Rundquist

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Observational Study ◽

Bowel Disease ◽

Quality Registry ◽

National Quality ◽

Inflammatory Bowel ◽

National Quality Registry

Download Full-text

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

Current Clinical Pharmacology ◽

10.2174/1574884715666200312100237 ◽

2020 ◽

Vol 15 (3) ◽

pp. 216-233 ◽

Cited By ~ 1

Author(s):

Maliha Naseer ◽

Shiva Poola ◽

Syed Ali ◽

Sami Samiullah ◽

Veysel Tahan

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Clinical Trials ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Effects ◽

Bowel Disease ◽

Relapse Prevention ◽

Remission Induction ◽

Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

Download Full-text

The Changing Prognosis of Ulcerative Colitis and Crohn’s Disease by Decades

Crohn's & Colitis 360 ◽

10.1093/crocol/otab008 ◽

2021 ◽

Author(s):

Burton I Korelitz ◽

Judy Schneider

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Medical Therapy ◽

Bowel Disease ◽

Surgical Intervention ◽

Inflammatory Bowel

Abstract We present a bird’s eye view of the prognosis for both ulcerative colitis and Crohn’s disease as contained in the database of an Inflammatory Bowel Disease gastroenterologist covering the period from 1950 until the present utilizing the variables of medical therapy, surgical intervention, complications and deaths by decades.

Download Full-text

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

Journal of Gastroenterology ◽

10.1007/s00535-021-01793-0 ◽

2021 ◽

Author(s):

Shinichiro Shinzaki ◽

Katsuyoshi Matsuoka ◽

Hiroki Tanaka ◽

Fuminao Takeshima ◽

Shingo Kato ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Potential Biomarker ◽

Adalimumab Therapy ◽

Adalimumab Treatment ◽

Inflammatory Bowel

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

Download Full-text