scholarly journals INCREASED TRAFFICKING OF MESENTERIC LYMPH-DERIVED γδ T CELLS INTO INTESTINAL MUCOSA IS ASSOCIATED WITH GUT INJURY AFTER INTESTINAL ISCHEMIA-REPERFUSION IN RATS

Lymphology ◽  
2019 ◽  
Vol 52 (2) ◽  
Author(s):  
J Yang ◽  
Y Shen ◽  
RQ Wu ◽  
H Zhu ◽  
Y Jin ◽  
...  
Keyword(s):  
T Cells ◽  
Intestinal Mucosa ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Γδ T Cells ◽  
Intestinal Injury ◽  
Endotoxin Concentration ◽  
Mesenteric Lymph ◽  
Tnf Α ◽  
Intestinal Ischemia Reperfusion

We sought to investigate the effects of mesenteric lymph-derived γδ T cells trafficking into intestinal mucosa on gut injury after intestinal ischemia-reperfusion (IIR). γδ T cells were separated from mesenteric lymph and then infused into the femoral vein of rats after the γδ T cells were labeled with 51Cr. Migration of γδ T cells in vivo across the intestinal mucosa was determined by γ-counter. Meanwhile, TNF-α activity and endotoxin concentration in mesenteric lymph were detected. The population of γδ T cells of Peyer's patches in the small intestines was analyzed by immunofluorescence double staining methods and flow cytometry. After IIR injury, the mean optical density value (MOD) and population of γδ T cells in Peyer's patches of the gut and migration of 51Cr-γδ T cells across the intestinal mucosa were significantly increased, which had highly positive correlations to degree of intestinal injury, TNF-α levels and endotoxin concentration in mesenteric lymph after reperfusion. The increased population of γδ T cells derived from mesenteric lymph trafficking into the intestinal mucosa might promote the small intestinal injury after IIR.

scholarly journals mtDNA-STING pathway promotes necroptosis-dependent enterocyte injury in intestinal ischemia reperfusion

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Xufei Zhang ◽  
Jie Wu ◽  
Qinjie Liu ◽  
Xuanheng Li ◽  
Sicheng Li ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Intestinal Barrier ◽  
Intestinal Injury ◽  
Tnf Α ◽  
Gut Homeostasis ◽  
Sting Pathway ◽  
Intestinal Ischemia Reperfusion ◽  
The Relationship

AbstractIntestinal ischemia reperfusion (I/R) injury is the important pathogenesis for acute intestinal barrier disruption. The STING signaling is associated with gut homeostasis and barrier integrity. However, the biological function and regulation of STING signaling in intestinal I/R injury are not yet fully understood. As the ligand of STING signaling, the mitochondrial DNA (mtDNA) has been found to be associated with necroptosis. It still remains unknown whether mtDNA-STING signaling triggers intestinal necroptosis in intestinal I/R injury. We found that circulating RIPK3 was significantly increased and had a positive correlation with markers of enterocyte injury in critically ill patients with intestinal injury. Moreover, the levels of circulating mtDNA were also associated with the levels of circulating RIPK3. To explore the relationship between mtDNA and intestinal necroptosis, mice were treated with the intraperitoneal injection of mtDNA, and necroptosis signaling was remarkably activated and the inhibition of necroptosis alleviated mtDNA-induced intestinal injury. Furthermore, STING knockout mice showed an alleviated intestinal necroptosis. In intestinal I/R injury, mtDNA was released from IECs and necroptosis was also triggered, companied with a significant decrease of RIPK3 in the intestine. STING knockout mice markedly attenuated intestinal necroptosis and intestinal I/R injury. Finally, we found that mtDNA-mediated STING signaling triggered necroptosis through synergistic IFN and TNF-α signaling in primary IECs. Our results indicated that mtDNA-STING signaling can contribute to intestinal I/R injury by promoting IEC necroptosis. STING-mediated both IFN and TNF-α signaling can trigger intestinal nercroptosis.

Characterization of γδ T Cells in Intestinal Mucosa From Patients With Early-Onset or Long-Standing Inflammatory Bowel Disease and Their Correlation With Clinical Status

2019 ◽  
Vol 13 (7) ◽  
pp. 873-883 ◽  
Author(s):  
Elena Lo Presti ◽  
Roberto Di Mitri ◽  
Filippo Mocciaro ◽  
Anna Barbara Di Stefano ◽  
Nunzia Scibetta ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Intestinal Mucosa ◽  
Bowel Disease ◽  
Early Onset ◽  
Γδ T Cells ◽  
Healthy Tissue ◽  
Effector Memory ◽  
Tnf Α ◽  
Inflammatory Bowel

Abstract Background and Aims Inflammatory bowel disease [IBD] is a complex chronic inflammatory disease of the human gut with no clear aetiology. Traditionally, dysregulated adaptive immune responses play an important role even though accumulating evidence suggests a role also for innate immunity. Because of the well-known plasticity of γδ T cells, we investigated their percentage occurrence, phenotypic features and effector functions in the intestinal mucosa of early-onset and long-standing IBD patients, as compared to healthy subjects. Methods Fresh biopsies from 30 Crohn’s disease and ulcerative colitis patients were obtained and digested, and cells were analysed by flow cytometry. Results We found a reduced frequency of Vδ1 T cells in tissue from early and late IBD patients (2.24% and 1.95%, respectively, vs 5.44% in healthy tissue) but an increased frequency of Vδ2 T cells in the gut of late IBD patients (3.19% in late patients vs 1.5% in early patients and 1.65% in healthy tissue). The infiltrating Vδ2 T cells had predominant effector memory and terminally differentiated phenotypes and produced elevated levels of tumour necrosis factor-α [TNF-α] and interleukin-17 [IL-17]. The frequency of tissue Vδ2 T cells correlated with the extent of the inflammatory response and the severity of IBD. Conclusion Our study shows that tissue Vδ1 T cells are decreased in IBD patients while Vδ2 T cells are increased in the gut of IBD patients and contribute to TNF-α production. Moreover, we identify an as yet unappreciated role of Vδ2 T cells in IL-17 production in the gut of long-standing IBD patients, suggesting that they also participate in the chronic inflammatory process.

Pharmacological enrollment of aldehyde dehydrogenase modulators to assist treating ischemia reperfusion-induced intestinal injury: is there a gap to be bridged?

2017 ◽  
Vol 131 (11) ◽  
pp. 1137-1140 ◽  
Author(s):  
Laurent Dollé
Keyword(s):  
Protective Effect ◽  
Aldehyde Dehydrogenase ◽  
Small Molecule ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Clinical Science ◽  
Intestinal Injury ◽  
Intestinal Ischemia Reperfusion ◽  
Near Future

This commentary highlights the research presented by Zhu et al. [1]. In this issue of the Clinical Science, the authors evaluated the protective effect of Alda-1 (a novel class of small molecule aldehyde dehydrogenase (ALDH2) activators) in the intestinal ischemia reperfusion (IR) injury. Remarkably, enhancing the ADLH2 activity by the use of Alda-1 can ameliorate several deleterious effects related to aldehydes, and may provide a better protection against an injury preestablished by IR. Together, an innovative metabolic strategy for treating patients with IR injury could be the use of ALDH modulators in a near future.

scholarly journals Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ozkan Onal ◽  
Fahri Yetisir ◽  
A. Ebru Salman Sarer ◽  
N. Dilara Zeybek ◽  
C. Oztug Onal ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Intestinal Injury ◽  
Control Group ◽  
Injury Score ◽  
Tissue Samples ◽  
Intestinal Ischemia Reperfusion

Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine.Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test.Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group.Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation.

scholarly journals Translocation of 99mTc labelled bacteria after intestinal ischemia and reperfusion

2004 ◽  
Vol 19 (4) ◽  
pp. 328-333 ◽  
Author(s):  
Samir Assi João ◽  
Suelene Suassuna Silvestre de Alencar ◽  
Aldo da Cunha Medeiros ◽  
Simone Otília Fernandes Diniz ◽  
Valbert Nascimento Cardoso ◽  
...  
Keyword(s):  
Bacterial Translocation ◽  
Intestinal Ischemia ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Ischemia And Reperfusion ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Colony Forming Units ◽  
Male Wistar Rats ◽  
Intestinal Ischemia Reperfusion

PURPOSE: Ischemia and reperfusion of the small intestine disrupts gut barrier, causes bacterial translocation and activates inflammatory responses. An experimental study was planned to evaluate if 99mTc labelled Escherichia coli translocates to mesenteric lymph nodes, liver, spleen, lung and serum of rats submitted to mesenteric ischemia/reperfusion. Additionally, it was observed if the time of reperfusion influences the level of translocation. METHODS: Forty male Wistar rats underwent 45 minutes of gut ischemia by occlusion of the superior mesenteric artery. The translocation of labelled bacteria to different organs and portal serum was determined in rats reperfused for 30 minutes, 24 hours, sham(S) and controls(C), using radioactivity count and colony forming units/g (CFU). RESULTS: All the organs from rats observed for 24 hours after reperfusion had higher levels of radioactivity and positive cultures (CFU) than did the organs of rats reperfused for 30 minutes, C and S, except in the spleen (p<0,01). CONCLUSION: The results of this study indicated that intestinal ischemia/reperfusion led to bacterial translocation, mostly after 24 hours of reperfusion.

scholarly journals TNF-α Induces Neutrophil Apoptosis Delay and Promotes Intestinal Ischemia-Reperfusion-Induced Lung Injury through Activating JNK/FoxO3a Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Daili Chen ◽  
Chaojin Chen ◽  
Xue Xiao ◽  
Ziyan Huang ◽  
Xiaolei Huang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Causative Factors ◽  
Tnf Α ◽  
Intestinal Ischemia Reperfusion ◽  
Injury Status

Background. Intestinal ischemia is a common clinical critical illness. Intestinal ischemia-reperfusion (IIR) leads to acute lung injury (ALI), but the causative factors of ALI are unknown. The aim of this study was to reveal the causative factors and mechanisms of IIR-induced lung injury. Methods. A mouse model of IIR was developed using C57BL/6 mice, followed by detection of lung injury status and plasma levels of inflammatory factors in sham-operated mice and model mice. Some model mice were treated with a tumor necrosis factor-α (TNF-α) inhibitor lenalidomide (10 mg/kg), followed by observation of lung injury status through hematoxylin and eosin staining and detection of neutrophil infiltration levels through naphthol esterase and Ly6G immunohistochemical staining. Additionally, peripheral blood polymorphonuclear neutrophils (PMNs) were cultured in vitro and then stimulated by TNF-α to mimic in vivo inflammatory stimuli; this TNF-α stimulation was also performed on PMNs after knockdown of FoxO3a or treatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125. PMN apoptosis after stimulation was detected using flow cytometry. Finally, the role of PMN apoptosis in IIR-induced lung injury was evaluated in vivo by detecting the ALI status in the model mice administered with ABT-199, a Bcl-2 inhibitor. Results. IIR led to pulmonary histopathological injury and increased lung water content, which were accompanied by increased plasma levels of inflammatory factors, with the TNF-α plasma level showing the most pronounced increase. Inhibition of TNF-α led to effective reduction of lung tissue injury, especially that of the damaging infiltration of PMNs in the lung. In vitro knockdown of FoxO3a or inhibition of JNK activity could inhibit TNF-α-induced PMN apoptosis. Further in vivo experiments revealed that ABT-199 effectively alleviated lung injury and decreased inflammation levels by promoting PMN apoptosis during IIR-induced lung injury. Conclusion. TNF-α activates the JNK/FoxO3a pathway to induce a delay in PMN apoptosis, which promotes IIR-induced lung injury.

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