scholarly journals TLRs in Hepatic Cellular Crosstalk

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Amelie E. Bigorgne ◽  
Ian Nicholas Crispe
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Parasitic Infections ◽  
Complex Environment ◽  
Hepatocellular Injury ◽  
Multiple Cell ◽  
Toxic Liver Damage ◽  
Exogenous Ligands

Toll-like receptors (TLRs) are expressed on all major subsets of liver cells. Both exogenous ligands derived from pathogens, and endogenous ligands that are products of cellular injury, engage these receptors and activate aspects of innate immunity. These receptors play a role in viral and parasitic infections of the liver, in ischemia-reperfusion injury, and in toxic liver damage, promoting antipathogen immunity but also hepatocellular injury and fibrogenesis. However, TLRs may also participate in negative feedback that limits tissue injury. In the complex environment of the liver, TLRs participate in pathologic cascades involving multiple cell types, manifesting their effects both through cell-autonomous actions, and via cellular crosstalk. In this paper we survey the involvement of TLRs in these diverse processes.

scholarly journals Myocardial Reperfusion Injury: Insights Gained from Gene-Targeted Mice

Physiology ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 303-308
Author(s):  
Steven P. Jones ◽  
David J. Lefer
Keyword(s):  
Reperfusion Injury ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Myocardial Cell ◽  
Myocardial Cell Injury ◽  
Multiple Cell ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia-reperfusion injury involves activation of multiple cell types, including leukocytes and endothelial cells. The pursuant inflammation involves diminished nitric oxide production, influx of neutrophils, and myocardial cell injury. Gene-targeted animals provide important clues about the progression of this inflammatory cascade.

scholarly journals Cell type- and tissue-specific functions of ecto-5′-nucleotidase (CD73)

2019 ◽  
Vol 317 (6) ◽  
pp. C1079-C1092 ◽  
Author(s):  
Marquet Minor ◽  
Karel P. Alcedo ◽  
Rachel A. Battaglia ◽  
Natasha T. Snider
Keyword(s):  
Cortical Plasticity ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Endothelial Permeability ◽  
Cell Types ◽  
Multiple Organ ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Organ Systems

Ecto-5′-nucleotidase [cluster of differentiation 73 (CD73)] is a ubiquitously expressed glycosylphosphatidylinositol-anchored glycoprotein that converts extracellular adenosine 5′-monophosphate to adenosine. Anti-CD73 inhibitory antibodies are currently undergoing clinical testing for cancer immunotherapy. However, many protective physiological functions of CD73 need to be taken into account for new targeted therapies. This review examines CD73 functions in multiple organ systems and cell types, with a particular focus on novel findings from the last 5 years. Missense loss-of-function mutations in the CD73-encoding gene NT5E cause the rare disease “arterial calcifications due to deficiency of CD73.” Aside from direct human disease involvement, cellular and animal model studies have revealed key functions of CD73 in tissue homeostasis and pathology across multiple organ systems. In the context of the central nervous system, CD73 is antinociceptive and protects against inflammatory damage, while also contributing to age-dependent decline in cortical plasticity. CD73 preserves barrier function in multiple tissues, a role that is most evident in the respiratory system, where it inhibits endothelial permeability in an adenosine-dependent manner. CD73 has important cardioprotective functions during myocardial infarction and heart failure. Under ischemia-reperfusion injury conditions, rapid and sustained induction of CD73 confers protection in the liver and kidney. In some cases, the mechanism by which CD73 mediates tissue injury is less clear. For example, CD73 has a promoting role in liver fibrosis but is protective in lung fibrosis. Future studies that integrate CD73 regulation and function at the cellular level with physiological responses will improve its utility as a disease target.

scholarly journals Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery

2020 ◽  
Vol 22 (1) ◽  
pp. 44
Author(s):  
Marc Micó-Carnero ◽  
Carlos Rojano-Alfonso ◽  
Ana Isabel Álvarez-Mercado ◽  
Jordi Gracia-Sancho ◽  
Araní Casillas-Ramírez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Microbial Populations ◽  
Operative Outcomes ◽  
Bidirectional Relationship ◽  
Preclinical And Clinical Studies ◽  
Different Cell Types ◽  
Stimulation Of

Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut–liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.

scholarly journals What we need to know about lipid-associated injury in case of renal ischemia-reperfusion

2018 ◽  
Vol 315 (6) ◽  
pp. F1714-F1719 ◽  
Author(s):  
Pauline Erpicum ◽  
Pascal Rowart ◽  
Jean-Olivier Defraigne ◽  
Jean-Marie Krzesinski ◽  
François Jouret
Keyword(s):  
Energy Demand ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Acid Oxidation ◽  
Metabolic Switch ◽  
Cell Functions ◽  
Associated Injury ◽  
Cortex Area

Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch toward anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting in a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is one of the major events of ROS-associated tissue injury. Here, we briefly review the current knowledge of renal cell lipid metabolism in normal and ischemic conditions. Next, we focus on renal lipid-associated injury, with emphasis on its mechanisms and consequences during the course of IRI. Finally, we discuss preclinical observations aiming at preventing and/or attenuating lipid-associated IRI.

Abstract 11710: Poloxamer 188 Protects Coronary Artery Endothelial Cells After Extended Hypoxia and Reoxygenation in an in vitro Model of Simulated Ischemia/Reperfusion Injury

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
zhu li ◽  
Matthew J Hampton ◽  
Matthew B Barajas ◽  
Matthias L Riess
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Calcium Influx ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Membrane Function ◽  
Ldh Release

Reperfusion restores blood flow after myocardial ischemia but can cause additional cellular injury by the sudden reintroduction of oxygen and nutrients. There is still no effective remedy for myocardial ischemia/reperfusion (IR) injury. Our previous study using cardiomyocytes (CMs) found that, after 3 hrs hypoxia followed by 2 hrs reoxygenation, viability decreased, and release of lactate dehydrogenase (LDH), calcium influx, membrane leakage (insertion of fluorescent probe FM1-43) significantly increased, indicating that cell membrane function was negatively affected. This was attenuated by the triblock copolymer Poloxamer (P)188. Here, we first hypothesized that endothelial cells are also susceptible to simulated IR injury, albeit requiring longer hypoxia times. We further hypothesized that P188 can also attenuate simulated IR injury in endothelial cells when given upon reoxygenation. Mouse coronary artery endothelial cells (MCAECs) were exposed to different durations of hypoxia (2, 3, 12 and 24 hrs) in serum- and glucose-free media +/- reoxygenation for 2 hrs in regular media. P188 was administered upon reoxygenation at 0, 100, 300 or 1,000 μM in experiments of 24 hrs hypoxia / 2 hrs reoxygenation. LDH release was measured and compared to appropriately timed normoxic control experiments. Reoxygenation and hypoxia times significantly longer than 3 hrs were required to elicit sufficient injury (panel A). When P188 was given upon reoxygenation after 24 hrs hypoxia, it dose-dependently attenuated LDH release (panel B). These findings contrast to the higher susceptibility of CMs to IR injury that only allowed shorter hypoxia durations. They also confirm a protective effect of P188 on the endothelium, not just on CMs. These findings have important implications for co-culture models with MCAECs and CMs to elucidate the interplay of both cell types on each other when studying mechanisms of cardioprotective strategies and compounds like P188.

Abstract 496: Genetic Neutrophil Deficiency Ameliorates Cerebral Ischemia-Reperfusion Injury

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ryan A Frieler ◽  
Yutein Chung ◽  
Jianrui Song ◽  
Thomas M Vigil ◽  
Richard M Mortensen
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Knockout Mice ◽  
Neutralizing Antibodies ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Artery Occlusion ◽  
Cross Reactivity

Background: Neutrophils respond rapidly to cerebral ischemia and are thought to contribute to inflammation-mediated injury during stroke. Neutralizing antibodies and inhibition of neutrophil chemotactic molecules can be protective during models of stroke, but many of these techniques have the potential to result in cross-reactivity and non-specificity with other immune cell types. Using myeloid Mcl1 knockout mice as a model of genetic neutrophil deficiency, we investigated the contribution of neutrophils to stroke pathophysiology. Methods: Myeloid Mcl1 knockout mice were subjected to transient 90-min middle cerebral artery occlusion and infarct size was assessed by MRI after 24 hours reperfusion. Immune cell mobilization and infiltration was assessed by flow cytometry after 24 hours reperfusion. Results: We found that myeloid Mcl1 knockout mice had significantly reduced infarct size when compared to heterozygous and wild type control mice (MyMcl1 +/+ : 78.0 mm 3 ; MyMcl1 +/- : 83.4 mm 3 ; MyMcl1 -/- : 55.1 mm 3 ). This was accompanied by a nearly complete absence of neutrophils in the ischemic hemisphere of myeloid Mcl1 knockout mice. Although myeloid Mcl1 knockout mice were protected from cerebral infarction, no significant differences in the expression of inflammatory genes were detected. Inhibition of neutrophil chemotaxis using CXCR2 pepducin treatment partially reduced neutrophil mobilization and recruitment to the brain after stroke, but did not reduce infarct size 24 hours after transient MCA occlusion. Conclusions: These data confirm that neutrophils have an important role in infarct development during stroke pathophysiology and suggest that complete deficiency, but not partial inhibition, is necessary to prevent neutrophil-mediated injury during stroke.

microRNA-223 promotes autophagy to aggravate lung ischemia-reperfusion injury by inhibiting the expression of transcription factor HIF2α

2020 ◽  
Vol 319 (1) ◽  
pp. L1-L10
Author(s):  
Chunlin Ye ◽  
Wanghong Qi ◽  
Shaohua Dai ◽  
Guowen Zou ◽  
Weicheng Liu ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Pulmonary Ventilation ◽  
Pulmonary Arteries ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Luciferase Reporter Gene ◽  
Gene Assay

Lung ischemia-reperfusion (I/R) injury severely endangers human health, and recent studies have suggested that certain microRNAs (miRNAs) play important roles in this pathological phenomenon. The current study aimed to ascertain the ability of miR-223 to influence lung I/R injury by targeting hypoxia-inducible factor-2α (HIF2α). First, mouse models of lung I/R injury were established: during surgical procedures, pulmonary arteries and veins and unilateral pulmonary portal vessels were blocked and resuming bilateral pulmonary ventilation, followed by restoration of bipulmonary ventilation. In addition, a lung I/R injury cell model was constructed by exposure to hypoxic reoxygenation (H/R) in mouse pulmonary microvascular endothelial cells (PMVECs). Expression of miR-223, HIF2α, and β-catenin in tissues or cells was determined by RT-qPCR and Western blot analysis. Correlation between miR-223 and HIF2α was analyzed by dual luciferase reporter gene assay. Furthermore, lung tissue injury and mouse PMVEC apoptosis was evaluated by hematoxylin and eosin (H&E), TUNEL staining, and flow cytometry. Autophagosomes in cells were detected by light chain 3 immunofluorescence assay. miR-223 was expressed at a high level while HIF2α/β-catenin was downregulated in tissues and cells with lung I/R injury. Furthermore, miR-223 targeted and repressed HIF2α expression to downregulate β-catenin expression. The miR-223/HIF2α/β-catenin axis aggravated H/R injury in mouse PMVECs and lung I/R injury in mice by enhancing autophagy. Taken together, miR-223 inhibits HIF2α to repress β-catenin, thus contributing to autophagy to complicate lung I/R injury. These findings provide a promising therapeutic target for treating lung I/R injury.

scholarly journals Inhibition of leukocyte L-selectin function with a monoclonal antibody attenuates reperfusion injury to the rabbit ear

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2322-2328 ◽  
Author(s):  
D Mihelcic ◽  
B Schleiffenbaum ◽  
TF Tedder ◽  
SR Sharar ◽  
JM Harlan ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Arterial Blood Flow ◽  
Arterial Blood ◽  
Rabbit Ear ◽  
Adhesive Interactions

Abstract The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive interactions with endothelial cells and is in part responsible for neutrophil rolling. We examined the role of L-selectin in ischemia- reperfusion injury of rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours with ambient temperature at 23 degrees C to 24 degrees C. Rabbits were treated at reperfusion with saline (n = 8), the L-selectin function-blocking LAM1–3 MoAb (2 mg/kg), or the nonfunction-blocking LAM1–14 MoAb (2 mg/kg). Tissue injury was determined by measuring edema and necrosis. Edema in the LAM1–3 MoAb- treated group (peak = 25 +/- 4 mL) was significantly less (P < .05) than in saline-treated (peak = 40 +/- 8 mL) and LAM1–14 MoAb-treated (peak = 41 +/- 6 mL) groups. Tissue necrosis at 7 days was not observed in the LAM1–3 MoAb-treated group, whereas significant necrosis (P < .05) was seen in the saline- (8% +/- 3% necrosis) and LAM1–14 MoAb- treated (7% +/- 3% necrosis) group. We conclude that blocking L- selectin ameliorates necrosis and edema after ischemia and reperfusion in the rabbit ear, presumably by blocking neutrophil rolling.

Role of leukocyte plugging and edema in skeletal muscle ischemia-reperfusion injury

1997 ◽  
Vol 273 (2) ◽  
pp. H989-H996 ◽  
Author(s):  
A. G. Harris ◽  
M. Steinbauer ◽  
R. Leiderer ◽  
K. Messmer
Keyword(s):  
Tissue Damage ◽  
Network Flow ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Capillary Density ◽  
Vessel Diameter ◽  
Cell Nuclei ◽  
Dorsal Skinfold Chamber ◽  
Tissue Edema

The purpose of this study was to examine the relationship of increased capillary network resistance due to leukocyte-capillary plugging and tissue edema through macromolecular leakage to tissue injury after ischemia-reperfusion (I/R). After a 3-h complete ischemia in the dorsal skinfold chamber of the awake Syrian hamster, the following parameters were measured: vessel diameter, macromolecular leakage, erythrocyte velocity, adherent leukocytes, rolling leukocytes, freely flowing leukocytes, functional capillary density (FCD), propidium iodide (PI)-positive cell nuclei, and increase in network flow resistance due to leukocyte-capillary plugging. These measurements were made under baseline conditions and after 0.5 and 2 h of reperfusion for I/R alone, I/R with phalloidin (PL) treatment (to block leakage), and I/R with both PL and cytochalasin D (CD) (to block both leakage and plugging). Neither treatment had an effect on the leukocyte adherence or rolling. PL treatment preserved the endothelial barrier, improved FCD, and reduced the amount of PI measured tissue damage. CD treatment eliminated the increase in network resistance due to leukocyte plugging but did not improve FCD or tissue damage. Thus, in this I/R model, macromolecular leakage plays a role in tissue injury, whereas leukocyte plugging does not appear to be an important mechanism.

scholarly journals Enhanced Effect of IL-1β-Activated Adipose-Derived MSCs (ADMSCs) on Repair of Intestinal Ischemia-Reperfusion Injury via COX-2-PGE2 Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Liu Liu ◽  
Yi Ren He ◽  
Shao Jun Liu ◽  
Lei Hu ◽  
Li Chuang Liang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Suppressive Effect ◽  
Signaling Axis ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Intestinal Ischemia Reperfusion

Adipose-derived mesenchymal stem cells (ADMSCs) have been used for treating tissue injury, and preactivation enhances their therapeutic effect. This study is aimed at investigating the therapeutic effect of activated ADMSCs by IL-1β on the intestinal ischaemia-reperfusion (IR) injury and exploring potential mechanisms. ADMSCs were pretreated with IL-1β in vitro, and activation of ADMSCs was assessed by α-SMA and COX-2 expressions and secretary function. Activated ADMSCs was transplanted into IR-injured intestine in a mouse model, and therapeutic effect was evaluated. In addition, to explore underlying mechanisms, COX-2 expression was silenced to investigate its role in activated ADMSCs for treatment of intestinal IR injury. When ADMSCs were pretreated with 50 ng/ml IL-1β for 24 hr, expressions of α-SMA and COX-2 were significantly upregulated, and secretions of PGE2, SDF-1, and VEGF were increased. When COX-2 was silenced, the effect of IL-1β treatment was abolished. Activated ADMSCs with IL-1β significantly suppressed inflammation and apoptosis and enhanced healing of intestinal IR injury in mice, and these effects were impaired by COX-2 silencing. The results of RNA sequencing suggested that compared with the IR injury group activated ADMSCs induced alterations in mRNA expression and suppressed the activation of the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways induced by intestinal IR injury, whereas silencing COX-2 impaired the suppressive effect of activated ADMSCs on these pathway activations induced by IR injury. These data suggested that IL-1β pretreatment enhanced the therapeutic effect of ADMSCs on intestinal IR injury repairing via activating ADMSC COX-2-PGE2 signaling axis and via suppressing the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways in the intestinal IR-injured tissue.

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