scholarly journals Plasma Corticotropin-Releasing Factor Receptors and B7-2+ Extracellular Vesicles in Blood Correlate with Irritable Bowel Syndrome Disease Severity

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 101 ◽  
Author(s):  
Shin-ichiro Hagiwara ◽  
Burcu Hasdemir ◽  
Melvin Heyman ◽  
Lin Chang ◽  
Aditi Bhargava
Keyword(s):  
Irritable Bowel Syndrome ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Stress Responses ◽  
Cell Types ◽  
Corticotropin Releasing Factor ◽  
Mouse Serum ◽  
Severity Scores ◽  
Health And Disease ◽  
Irritable Bowel

Extracellular vesicles (EVs) are composed of bilayer membranes that are released by different cell types and are present in bodily fluids, such as blood, urine, and bile. EVs are thought to play a key role in intracellular communication. Based on their size and density, EVs are classified into small, medium, or large EVs. Cargo composition in EVs reflects physiological changes in health and disease. Patients with irritable bowel syndrome (IBS) exhibit visceral hypersensitivity and mood disorders. Stressful episodes often precede disease symptoms in IBS patients. Stress-induced symptoms include, but are not limited to, abdominal pain and mood swings. Perceived stress responses are mediated by two known G protein-coupled receptors (GPCRs), corticotropin-releasing factor receptor 1 and 2 (CRFRs). CRFRs belong to the Class B secretin receptor family of GPCRs. Here, we show that CRFRs were present in human and murine plasma, and in EVs purified from mouse serum. CRFRs were present in plasma from IBS patients and healthy controls. EVs secreted from immune cells influence both adaptive and innate immune responses via exchange of EVs between different immune cell types. B7-2 (CD86), a plasma membrane antigen-presenting protein, is present on EVs secreted from dendritic, B-, and mast cells, whereas CD9 is present on EVs secreted from dendritic and intestinal epithelial cells. We found that plasma CRFR levels positively correlated with B7-2+ EVs (R = 0.8597, p < 0.0001), but no association was seen with CD9+ EVs. Plasma CRFRs expression negatively correlated with IBS severity scores. Our data suggests that plasma EVs from immune cells carry CRFRs as cargos and influence cell-cell communication in health and disease.

scholarly journals Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

2018 ◽  
Vol 9 ◽  
Author(s):  
Mahanand Chatoo ◽  
Yi Li ◽  
Zhiqiang Ma ◽  
John Coote ◽  
Jizeng Du ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Immune Cells ◽  
Corticotropin Releasing Factor ◽  
Irritable Bowel

scholarly journals Su1581 – Gpcr-Containing B7-2+ Extracellular Vesicles from Immune Cells in Blood Correlate with Irritable Bowel Syndrome Severity

2019 ◽  
Vol 156 (6) ◽  
pp. S-571
Author(s):  
Shin-ichiro Hagiwara ◽  
Burcu Hasdemir ◽  
Melvin B. Heyman ◽  
Lin Chang ◽  
Aditi Bhargava
Keyword(s):  
Irritable Bowel Syndrome ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Irritable Bowel

scholarly journals Overexpression of corticotropin-releasing factor in intestinal mucosal eosinophils is associated with clinical severity in Diarrhea-Predominant Irritable Bowel Syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eloísa Salvo-Romero ◽  
Cristina Martínez ◽  
Beatriz Lobo ◽  
Bruno K. Rodiño-Janeiro ◽  
Marc Pigrau ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Life Stress ◽  
Secretory Activity ◽  
Corticotropin Releasing Factor ◽  
Clinical Severity ◽  
Jejunal Mucosa ◽  
Gut Dysfunction ◽  
Transmission Electron ◽  
Activation Profile ◽  
Irritable Bowel

AbstractCorticotropin-releasing factor (CRF) has been identified in intestinal mucosal eosinophils and associated with psychological stress and gut dysfunction. Irritable bowel syndrome (IBS) is commonly characterized by altered intestinal motility, immune activation, and increased gut barrier permeability along with heightened susceptibility to psychosocial stress. Despite intensive research, the role of mucosal eosinophils in stress-associated gut dysfunction remains uncertain. In this study, we evaluated eosinophil activation profile and CRF content in the jejunal mucosa of diarrhea-predominant IBS (IBS-D) and healthy controls (HC) by gene/protein expression and transmission electron microscopy. We also explored the association between intestinal eosinophil CRF and chronic stress, and the potential mechanisms underlying the stress response by assessing eosinophil response to neuropeptides. We found that mucosal eosinophils displayed higher degranulation profile in IBS-D as compared to HC, with increased content of CRF in the cytoplasmic granules, which significantly correlated with IBS clinical severity, life stress background and depression. Eosinophils responded to substance P and carbachol by increasing secretory activity and CRF synthesis and release, without promoting pro-inflammatory activity, a profile similar to that found in mucosal eosinophils from IBS-D. Collectively, our results suggest that intestinal mucosal eosinophils are potential contributors to stress-mediated gut dysfunction through CRF production and release.

scholarly journals Corticotropin-Releasing Factor and Toll-Like Receptor Gene Expression Is Associated with Low-Grade Inflammation in Irritable Bowel Syndrome Patients with Depression

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Song Jizhong ◽  
Wang Qiaomin ◽  
Wang Chao ◽  
Li Yanqing
Keyword(s):  
Gene Expression ◽  
Irritable Bowel Syndrome ◽  
Inflammatory Response ◽  
Psychiatric Symptoms ◽  
Corticotropin Releasing Factor ◽  
Low Grade ◽  
Lower Grade ◽  
Toll Like Receptor ◽  
Irritable Bowel ◽  
Low Grade Inflammation

The mechanism of low-grade inflammation in irritable bowel syndrome (IBS) is unclear; our research concentrates on the involvement of the corticotropin-releasing factor (CRF) and Toll-like receptor (TLR) gene expression in the process of low-grade inflammation in IBS patients with depression. This study suggests more IBS patients are presenting with the states of depression and anxiety. IBS patients with depression have shown a lower grade inflammatory response and an imbalance of the inflammatory response. CRF1, CRF2, TLR2, and TLR4 in IBS patients with depression are significantly higher than those without depression and controls. Thus, activation of the CRF-TLR associated pathways produces an inflammatory reaction, which can concurrently affect the digestive tract and the CNS and induce the corresponding digestive and psychiatric symptoms.

scholarly journals The Role of Brain-Derived Neurotrophic Factor in Irritable Bowel Syndrome

2021 ◽  
Vol 11 ◽  
Author(s):  
Thomas Jan Konturek ◽  
Cristina Martinez ◽  
Beate Niesler ◽  
Ivo van der Voort ◽  
Hubert Mönnikes ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Symptom Severity ◽  
Neurotrophic Factor ◽  
Mrna Levels ◽  
Bdnf Mrna ◽  
Protein Levels ◽  
Severity Scores ◽  
Descending Colon ◽  
Irritable Bowel

Several studies have implied a role of brain-derived neurotrophic factor (BDNF) in abdominal pain modulation in irritable bowel syndrome (IBS). The aim of this study was to establish BDNF protein expression in human colonic biopsies and to show variation in IBS compared to controls. BDNF protein and mRNA levels were correlated with IBS symptom severity based on the IBS-symptom severity score (IBS-SSS). Biopsies from the descending colon and IBS-SSS were obtained from 10 controls and 20 IBS patients. Total protein of biopsies was extracted and assessed by ELISA and Western Blot. Total mRNA was extracted and gene expression measured by nCounter analysis. In IBS patients, symptom severity scores ranged from 124 to 486 (mean ± sem: 314.2 ± 21.2, &gt;300 represents severe IBS) while controls ranged from 0 to 72 (mean ± sem: 27.7 ± 9.0, &lt;75 represents healthy subjects, p &lt; 0.001). IBS patients reported significantly more food malabsorption, former abdominal surgery and psychiatric comorbidities. BDNF protein was present in all samples and did not differ between IBS and controls or sex. Subgroup analysis showed that female IBS patients expressed significantly more BDNF mRNA compared to male patients (p &lt; 0.05) and male IBS-D patients had higher IBS symptom severity scores and lower BDNF mRNA and protein levels compared to male controls (p &lt; 0.05). Scatter plot showed a significant negative correlation between IBS-SSS and BDNF mRNA levels in the cohort of male IBS-D patients and their male controls (p &lt; 0.05). We detected a high proportion of gastrointestinal surgery in IBS patients and confirmed food intolerances and psychiatric diseases as common comorbidities. Although in a small sample, we demonstrated that BDNF is detectable in human descending colon, with higher BDNF mRNA levels in female IBS patients compared to males and lower mRNA and protein levels in male IBS-D patients compared to male controls. Further research should be directed toward subgroups of IBS since their etiologies might be different.

scholarly journals Do corticotropin releasing factor-1 receptors influence colonic transit and bowel function in women with irritable bowel syndrome?

2009 ◽  
Vol 296 (6) ◽  
pp. G1299-G1306 ◽  
Author(s):  
Seth Sweetser ◽  
Michael Camilleri ◽  
Sara J. Linker Nord ◽  
Duane D. Burton ◽  
Lorna Castenada ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Colonic Motility ◽  
Bowel Function ◽  
Colonic Transit ◽  
Corticotropin Releasing Factor ◽  
Analysis Of Covariance ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Safety Issues ◽  
Irritable Bowel

Corticotropin releasing factor (CRF), a mediator of stress response, alters gastrointestinal (GI) functions. Stress-related changes in colonic motility are blocked by selective CRF1 receptor antagonists. Our aim was to assess whether modulation of central and peripheral CRF1 receptors affects colonic transit and bowel function in female patients with diarrhea-predominant irritable bowel syndrome (D-IBS). This randomized, double-blind, placebo-controlled, 2-wk study evaluated the effects of oral pexacerfont (BMS-562086), a selective CRF1 receptor antagonist, 25 and 100 mg qd, on GI and colonic transit of solids [by validated scintigraphy with primary end point colonic geometric center (GC) at 24 h] and bowel function (by validated daily diaries) in 39 women with D-IBS. The 100-mg dose was comparable to a dose that inhibited colonic motility in stressed rats. Treatment effects were compared by analysis of covariance with baseline colonic transit as covariate. The study had 80% power (α = 0.05) to detect clinically meaningful (26%) differences in colonic transit. Thirty-nine of 55 patients fulfilled eligibility criteria (9 screen failures, 5 baseline GC24 outside prespecified range). At baseline, three treatment groups had comparable age, body mass index, and GC 24 h. Significant effects of pexacerfont relative to placebo were not detected on colonic GC24 ( P = 0.53), gastric emptying, orocecal transit, ascending colon emptying half-time, and stool frequency, consistency, and ease of passage. No safety issues were identified. We conclude that in women with D-IBS, pexacerfont, 25 or 100 mg qd, does not significantly alter colonic or other regional transit or bowel function. The role of central and peripheral CRF1 receptors in bowel function in D-IBS requires further study.

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