Inflammasome-Dependent Peroxiredoxin 2 Secretion Induces the Classical Complement Pathway Activation

Park, Cheol Ho; Lee, Hyun Sook; Kwak, Man Sup; Shin, Jeon Soo

doi:10.4110/in.2021.21.e36

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…Prxs have been increasingly associated with regulation of inflammasomes. Activation of inflammasomes NLRP3, NLRC4 or AIM2 in murine macrophages in vitro caused secretion of Prx1, Prx2, Prx5 and Prx6 [ 84 ]. Downregulation of Prx1 was suggested to transcriptionally inhibit NLRP3 inflammasome expression in intestinal inflammation [ 85 ].…”

Section: Prx4 and Inflammationmentioning

confidence: 99%

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer

et al. 2022

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Peroxiredoxin IV (Prx4) is a 2-Cysteine peroxidase with ubiquitous expression in human tissues. Prx4 scavenges hydrogen peroxide and participates in oxidative protein folding in the endoplasmic reticulum. In addition, Prx4 is secreted outside the cell. Prx4 is upregulated in several cancers and is a potential therapeutic target. We have summarized historical and recent advances in the structure, function and biological roles of Prx4, focusing on inflammatory diseases and cancer. Oxidative stress is known to activate pro-inflammatory pathways. Chronic inflammation is a risk factor for cancer development. Hence, redox enzymes such as Prx4 are important players in the crosstalk between inflammation and cancer. Understanding molecular mechanisms of regulation of Prx4 expression and associated signaling pathways in normal physiological and disease conditions should reveal new therapeutic strategies. Thus, although Prx4 is a promising therapeutic target for inflammatory diseases and cancer, further research needs to be conducted to bridge the gap to clinical application.

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Section: Prx4 and Inflammationmentioning

confidence: 99%

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer

et al. 2022

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“…The inflammasome is a caspase-1-activating intracellular protein complex that induces the maturation and release of critical proinflammatory cytokines IL-1β and IL-18 ( 15 16 ). Inflammasome formation is initiated by several pattern recognition receptors, among which NLR family pyrin domain containing 3 (NLRP3) can be activated by diverse abnormal pathogen- or host-derived factors, such as microbial components or endogenous metabolites and stress signals, respectively ( 17 18 ).…”

Section: Introductionmentioning

confidence: 99%

Extracellular Acidification Augments NLRP3-Mediated Inflammasome Signaling in Macrophages

et al. 2023

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Inflammation is a series of host defense processes in response to microbial infection and tissue injury. Inflammatory processes frequently cause extracellular acidification in the inflamed region through increased glycolysis and lactate secretion. Therefore, the immune cells infiltrating the inflamed region encounter an acidic microenvironment. Extracellular acidosis can modulate the innate immune response of macrophages; however, its role for inflammasome signaling still remains elusive. In the present study, we demonstrated that macrophages exposed to an acidic microenvironment exhibited enhanced caspase-1 processing and IL-1β secretion compared with those under physiological pH. Moreover, exposure to an acidic pH increased the ability of macrophages to assemble the NLR family pyrin domain containing 3 (NLRP3) inflammasome in response to an NLRP3 agonist. This acidosis-mediated augmentation of NLRP3 inflammasome activation occurred in bone marrow-derived macrophages but not in bone marrow-derived neutrophils. Notably, exposure to an acidic environment caused a reduction in the intracellular pH of macrophages but not neutrophils. Concordantly, macrophages, but not neutrophils, exhibited NLRP3 agonist-mediated translocation of chloride intracellular channel protein 1 (CLIC1) into their plasma membranes under an acidic microenvironment. Collectively, our results demonstrate that extracellular acidosis during inflammation can increase the sensitivity of NLRP3 inflammasome formation and activation in a CLIC1-dependent manner. Thus, CLIC1 may be a potential therapeutic target for NLRP3 inflammasome-mediated pathological conditions.

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“…Lytic erythrocytes and damaged neurons can release Prx2. Thus, extracellular Prx2 activates microglia and promotes neuronal apoptosis [ 9 , 10 ]. In this study, we analyzed the content of Prx2 in the CSF and the blood of SAH patients by an enzyme-linked immunosorbent assay (ELISA) and found that Prx2 can be used as a biomarker for judging the clinical status of the patients.…”

Section: Introductionmentioning

confidence: 99%

Peroxiredoxin 2 Is a Potential Objective Indicator for Severity and the Clinical Status of Subarachnoid Hemorrhage Patients

Peng

Pang

et al. 2023

Disease Markers

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Purpose. We have demonstrated that peroxiredoxin 2 (Prx2) released from lytic erythrocytes and damaged neurons into the subarachnoid space could activate microglia and then result in neuronal apoptosis. In this study, we tested the possibility of using Prx2 as an objective indicator for severity of the subarachnoid hemorrhage (SAH) and the clinical status of the patient. Materials and Methods. SAH patients were prospectively enrolled and followed up for 3 months. Cerebrospinal fluid (CSF) and blood samples were collected 0-3 and 5-7 days after SAH onset. The levels of Prx2 in the CSF and the blood were measured by an enzyme-linked immunosorbent assay (ELISA). We used Spearman’s rank coefficient to assess the correlation between Prx2 and the clinical scores. Receiver operating characteristic (ROC) curves were used for Prx2 levels to predict the outcome of SAH by calculating the area under the curve (AUC). Unpaired Student’s t -test was used to analyze the differences in continuous variables across cohorts. Results. Prx2 levels in the CSF increased after onset while those in the blood decreased. Existing data showed that Prx2 levels within 3 days in the CSF after SAH were positively correlated with the Hunt-Hess score ( R = 0.761 , P < 0.001 ). Patients with CVS had higher levels of Prx2 in their CSF within 5-7 days after onset. Prx2 levels in the CSF within 5-7 days can be used as a predictor of prognosis. The ratio of Prx2 in the CSF and the blood within 3 days of onset was positively correlated with the Hunt-Hess score and negatively correlated with Glasgow Outcome Scale (GOS; R = ‐ 0.605 , P < 0.05 ). Conclusion. We found that the levels of Prx2 in the CSF and the ratio of Prx2 in the CSF and the blood within 3 days of onset can be used as a biomarker to detect the severity of the disease and the clinical status of the patient.

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Inflammasome-Dependent Peroxiredoxin 2 Secretion Induces the Classical Complement Pathway Activation

Cited by 7 publications

References 41 publications

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer

Extracellular Acidification Augments NLRP3-Mediated Inflammasome Signaling in Macrophages

Peroxiredoxin 2 Is a Potential Objective Indicator for Severity and the Clinical Status of Subarachnoid Hemorrhage Patients

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