scholarly journals Suppression of PTRF Alleviates Post-Infectious Irritable Bowel Syndrome via Downregulation of the TLR4 Pathway in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui-hui Zhou ◽  
Ye-ming Zhang ◽  
Sheng-peng Zhang ◽  
Qi-xiang Xu ◽  
Ya-qing Tian ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Water Content ◽  
Inos Expression ◽  
Tlr4 Signaling ◽  
Fecal Water ◽  
Irritable Bowel ◽  
Post Infectious

Background: Accumulating evidence suggests that the polymerase I and transcript release factor (PTRF), a key component of the caveolae structure on the plasma membrane, plays a pivotal role in suppressing the progression of colorectal cancers. However, the role of PTRF in the development of functional gastrointestinal (GI) disorders remains unclear. Post-infectious irritable bowel syndrome (PI-IBS) is a common functional GI disorder that occurs after an acute GI infection. Here, we focused on the role of PTRF in the occurrence of PI-IBS and investigated the underlying mechanisms.Methods: Lipopolysaccharide (LPS) (5 μg/ml) was used to induce inflammatory injury in human primary colonic epithelial cells (HCoEpiCs). Furthermore, a rat model of PI-IBS was used to study the role of PTRF. Intestinal sensitivity was assessed based on the fecal water content. A two-bottle sucrose intake test was used to evaluate behavioral changes. Furthermore, shRNA-mediated knockdown of PTRF was performed both in vitro and in vivo. We detected the expression of PTRF in colonic mucosal tissues through immunohistochemistry (IHC), western blotting (WB), and immunofluorescence (IF) analysis. Luciferase activity was quantified using a luciferase assay. Co-localization of PTRF and Toll-like receptor 4 (TLR4) was detected using IF analysis. The activation of the signaling pathways downstream of TLR4, including the iNOs, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) pathways, was detected via WB. The levels of NO, IL-1β, IL-6, and TNF-α were measured using enzyme-linked immunosorbent assays.Results: LPS significantly induced PTRF expression and signaling downstream of TLR4, including p38, ERK, and JNK pathways, in HCoEpiCs. Moreover, shRNA-mediated knockdown of PTRF in HCoEpiCs significantly decreased the phosphorylation of JNK, ERK, and p38 and iNOS expression. In PI-IBS rats, the lack of PTRF not only reduced fecal water content and suppressed depressive behavior but also increased the body weight. Furthermore, we found a strong co-localization pattern for PTRF and TLR4. Consistently, the lack of PTRF impaired TLR4 signaling, as shown by the decreased levels of p-JNK, p-ERK, and p-p38, which are upstream factors involved in iNOS expression.Conclusion: PTRF promoted PI-IBS and stimulated TLR4 signaling both in vitro and in vivo. The results of this study not only enlighten the pathogenesis of PI-IBS but also help us understand the biological activity of PTRF and provide an important basis for the clinical treatment of PI-IBS by targeting PTRF.

scholarly journals Prokaryotic and Eukaryotic Fecal Microbiota in Irritable Bowel Syndrome Patients and Healthy Individuals Colonized With Blastocystis

2021 ◽  
Vol 12 ◽  
Author(s):  
Céline Nourrisson ◽  
Julien Scanzi ◽  
Julie Brunet ◽  
Frédéric Delbac ◽  
Michel Dapoigny ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
High Throughput Sequencing ◽  
Fecal Microbiota ◽  
Healthy Individuals ◽  
High Prevalence ◽  
Potential Link ◽  
Irritable Bowel

Blastocystis is the most frequently isolated protozoan from human stool. Its role in human health is still debated, and a high prevalence was reported in irritable bowel syndrome (IBS) subjects, suggesting a potential link with microbiota. In the present study, we aimed to investigate prokaryotic and eukaryotic microbiota in both IBS-C (constipated) and healthy individuals. We recruited 35 IBS-C patients and 23 healthy subjects, from which 12 and 11 carried Blastocystis, respectively. We performed 16S and 18S rRNA high-throughput sequencing on feces. Whereas we did not observe differences between infected and non-infected controls, several phyla were significantly modified in IBS-C patients according to the presence of Blastocystis. Tenericutes phylum and Ruminococcaceae family were especially increased in Blastocystis carriers. Furthermore, colonization with Blastocystis was associated with discrete changes in the microbial eukaryome, particularly among the Fungi taxa. Depending on the group of patients considered, the mycobiota changes do not go in the same direction and seem more deleterious in the IBS-C group. These results encourage further in vivo and in vitro investigations concerning the role of Blastocystis in the gut environment.

NaHS inhibits NF-κB signal against inflammation and oxidative stress in post-infectious irritable bowel syndrome

RSC Advances ◽  
2016 ◽  
Vol 6 (69) ◽  
pp. 64208-64214 ◽  
Author(s):  
Shenglan Yang ◽  
Danfang Deng ◽  
Yingying Luo ◽  
Yanran Wu ◽  
Rui Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Irritable Bowel Syndrome ◽  
Hydrogen Sulfide ◽  
Murine Model ◽  
Irritable Bowel ◽  
And Oxidative Stress ◽  
Post Infectious

In this study, the alleviating role of hydrogen sulfide (H2S) was investigated in a Post-Infectious Irritable Bowel Syndrome (PI-IBS) murine model and Caco-2 cells.

scholarly journals Role of miR-148a in Mitigating Hepatic Ischemia-Reperfusion Injury by Repressing the TLR4 Signaling Pathway via Targeting CaMKIIα in Vivo and in Vitro

2018 ◽  
Vol 49 (5) ◽  
pp. 2060-2072 ◽  
Author(s):  
Daofeng Zheng ◽  
Zhongtang Li ◽  
Xufu Wei ◽  
Rui Liu ◽  
Ai Shen ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Hepatic Ischemia ◽  
Tlr4 Signaling ◽  
Hepatic Ischemia Reperfusion

Background/Aims: Hepatic ischemia-reperfusion (I/R) injury, which is mainly induced by inflammation and unstable intracellular ions, is a major negative consequence of surgery that compromises hepatic function. However, the exact mechanisms of liver I/R injury have not been determined. Positive crosstalk with the Ca2+/CaMKII pathway is required for complete activation of the TLR4 pathway and inflammation. We previously found that miR-148a, which decreased in abundance with increasing reperfusion time, targeted and repressed the expression of CaMKIIα. In the present study, we examined the role of the miR-148a machinery in I/R-induced Ca2+/CaMKII and TLR4 signaling changes, inflammation, and liver dysfunction in vivo and in vitro. Methods: Liver function was evaluated by serum aminotransferase levels and hematoxylin-eosin (HE) staining. Inflammatory factors were detected by enzyme-linked immunosorbent assay. Gene and protein expression were assessed by RT-PCR and western blot. Small interfering RNA was used to silence target gene expression. HE staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to measure hepatic tissue apoptosis. These assays were performed to identify factors upregulated in hepatic I/R injury and downregulated by miR-148a. Results: We manifested that expression of CaMKIIα and phosphorylation of TAK1 and IRF3 were elevated in hypoxia/reoxygenation (H/R)-treated primary Kupffer cells (KCs) and liver tissue of I/R-treated mice, but these effects were attenuated by treatment with miR-148a mimic and were accompanied by the alleviation of liver dysfunction and hepatocellular apoptosis. Luciferase reporter experiments showed that miR148a suppressed luciferase activity by almost 60%. Moreover, knockdown of CaMKIIα in H/R KCs led to significant deficiencies in p-TAK1, P-IRF3, IL-6, and TNF-α, which was consistent with the effects of miR-148a overexpression. Otherwise, the same trend of activation of TAK1 and IRF3 and inflammatory factors in vitro was observed in the siTAK1 + siIRF3 group compared with the siCaMKIIα group. Conclusion: Taken together, we conclude that miR-148a may mitigate hepatic I/R injury by ameliorating TLR4-mediated inflammation via targeting CaMKIIα in vitro and in vivo.

Probiotic Agents in the Treatment of Irritable Bowel Syndrome

2007 ◽  
Vol 35 (5) ◽  
pp. 583-589 ◽  
Author(s):  
M Guslandi
Keyword(s):  
Irritable Bowel Syndrome ◽  
Critical Evaluation ◽  
Bacterial Overgrowth ◽  
Small Intestinal Bacterial Overgrowth ◽  
Serotonin System ◽  
Small Intestinal ◽  
Irritable Bowel ◽  
Inflammatory Changes ◽  
Post Infectious

Irritable bowel syndrome (IBS) is characterized by abdominal pain and alterations in bowel habits. Several pathogenetic factors, such as altered intestinal motility, visceral hypersensitivity, serotonin system abnormalities and psychic disturbances have been identified. Recently, a pathogenetic role of intestinal microflora has been shown in IBS: viral or bacterial infection can trigger post-infectious IBS; some patients have small intestinal bacterial overgrowth; the composition of patients' enteric flora is altered; and minimal inflammatory changes, consistent with the pro-inflammatory role of bacteria, have been demonstrated. Probiotics may, therefore, offer a rational therapeutic approach to IBS. The data available on the use of probiotics in IBS are still limited and results of controlled clinical trials are contradictory because they have been performed using different species, dosages, treatment durations and end-points for results evaluation. A critical evaluation of the therapeutic role of the various probiotics in IBS is presented in this article.

scholarly journals Increased Vδ1γδT cells Predominantly Contributed to IL-17 Production in the Development of Adult Human Post-infectious Irritable Bowel Syndrome

2020 ◽  
Author(s):  
liwei dong ◽  
xiaoning sun ◽  
zhichao ma ◽  
jiao fu ◽  
fujin liu ◽  
...  
Keyword(s):  
T Cells ◽  
Irritable Bowel Syndrome ◽  
Peripheral Blood ◽  
Γδ T Cells ◽  
Γδt Cells ◽  
Peripheral T Cells ◽  
Confocal Fluorescence ◽  
Irritable Bowel ◽  
Post Infectious

Abstract Background: γδT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that γδT cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study’s aim is to investigate the functionally predominant subset and its role in PI-IBS. Methods: The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 γδ T cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method. and cultured, functionally evaluated by CCK-8 assay (proliferation)，CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively.Results: 1. Vδ1 γδ T cells significantly increased while Vδ2 γδ T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (P<0.05). 2. When cultured in vitro, the Vδ1 γδ T cells remarkably proliferated, activated and produced IL-17 (P<0.05). Conclusions: Our results suggest that Vδ1 γδ T cells was the predominant γδ T cells subset in both peripheral and intestinal tissue, and was the major IL-17 producing γδ T cells in PI-IBS.

scholarly journals Increased Vδ1 γδT cells Predominantly Contributed to IL-17 Production in the Development of Adult Human Post-infectious Irritable Bowel Syndrome

2020 ◽  
Author(s):  
liwei dong ◽  
xiaoning sun ◽  
zhichao ma ◽  
jiao fu ◽  
fujin liu ◽  
...  
Keyword(s):  
T Cells ◽  
Irritable Bowel Syndrome ◽  
Peripheral Blood ◽  
Γδ T Cells ◽  
Γδt Cells ◽  
Peripheral T Cells ◽  
Confocal Fluorescence ◽  
Irritable Bowel ◽  
Post Infectious

Abstract Background: γδT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that γδT cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study’s aim is to investigate the functionally predominant subset and its role in PI-IBS. Methods: The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 γδT cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method. and cultured, functionally evaluated by CCK-8 assay (proliferation)，CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively. Results: 1. Vδ1 γδ T cells significantly increased while Vδ2 gd T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (P<0.05). 2. When cultured in vitro, the Vδ1 gd T cells remarkably proliferated, activated and produced IL-17 (P<0.05）. Conclusions: Our results suggest that Vδ1 γδ T cells was the predominant γδ T cells subset in both peripheral and intestinal tissue, and was the major IL-17 producing γδ T cells in PI-IBS.

The Role of Acupuncture on the Gut–Brain–Microbiota Axis in Irritable Bowel Syndrome

2021 ◽  
pp. 1-30
Author(s):  
Kiangyada Yaklai ◽  
Sintip Pattanakuhar ◽  
Nipon Chattipakorn ◽  
Siriporn C. Chattipakorn
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Clinical Studies ◽  
Work Productivity ◽  
Action Mechanisms ◽  
Wide Range ◽  
Potential Link ◽  
Irritable Bowel

Irritable bowel syndrome (IBS) is a chronic dysfunction of the gastrointestinal tract, commonly characterized by abdominal pain or abdominal discomfort. These symptoms can substantially reduce the quality of life and work productivity of the patients. The exact pathogenesis of IBS remains unclear, as it has become apparent that multiple pathways are activated in the condition, including inflammation, immunology, neurology and psychology. Recent evidence has shown that symptoms in IBS are related to the dysfunction of the nervous system, particularly the viscerosomatic pathway, through immune-to-brain communication. The potential link between brain–gut relationships is gut microbiota. The management of IBS mostly focuses on symptomatically treating the patients. There are a wide range of standard treatments, including pharmacological to psychological interventions which are effective in some patients. Therefore, a combination of therapies including both standard and complimentary treatments, including Traditional Chinese Medicine (TCM) such as acupuncture, have been used in treating IBS patients. Several in vivo and clinical studies have demonstrated the efficacy of acupuncture in treating IBS. Increasing attention has been paid to research regarding the action mechanisms of acupuncture for IBS. This paper summarizes and discusses the possible mechanisms associated with acupuncture on the pathophysiology of IBS, including gastrointestinal (GI) motility, visceral hypersensitivity, the immune system, neurotransmitters, and the brain–gut axis. The results fromin vivo and clinical studies have been included. In addition, the effects of acupuncture on gut microbiota in IBS are included and any contradictory findings are deliberated.

scholarly journals Increased Vδ1 γδT cells Predominantly Contributed to IL-17 Production in the Development of Adult Human Post-infectious Irritable Bowel Syndrome

2020 ◽  
Author(s):  
liwei dong ◽  
xiaoning sun ◽  
zhichao ma ◽  
jiao fu ◽  
fujin liu ◽  
...  
Keyword(s):  
T Cells ◽  
Irritable Bowel Syndrome ◽  
Peripheral Blood ◽  
Colonic Tissue ◽  
Γδt Cells ◽  
Peripheral T Cells ◽  
Confocal Fluorescence ◽  
Irritable Bowel ◽  
Post Infectious

Abstract Background: gdT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that gd T cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study’s aim is to investigate the functionally predominant subset and its role in PI-IBS. Methods: The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 gd T cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method. and cultured, functionally evaluated by CCK-8 assay (proliferation), CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively.Results: 1. Vδ1 gd T cells significantly increased while Vδ2 gd T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (P<0.05). 2. When cultured in vitro, the Vδ1 gd T cells remarkably proliferated, activated and produced IL-17 (P<0.05).Conclusions: Our results suggest that Vδ1 gd T cells was the predominant gd T cells subset in both peripheral and intestinal tissue, and was the major IL-17 producing gd T cells in PI-IBS.

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