scholarly journals Extracellular CIRP Induces Macrophage Extracellular Trap Formation Via Gasdermin D Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yongchan Lee ◽  
Bridgette Reilly ◽  
Chuyi Tan ◽  
Ping Wang ◽  
Monowar Aziz
Keyword(s):  
Rna Binding ◽  
Tissue Injury ◽  
Time Lapse ◽  
Extracellular Dna ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Trap Formation ◽  
Caspase 1 ◽  
Extracellular Trap

Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern promoting inflammation and tissue injury. During bacterial or viral infection, macrophages release DNA decorated with nuclear and cytoplasmic proteins known as macrophage extracellular traps (METs). Gasdermin D (GSDMD) is a pore-forming protein that has been involved in extracellular trap formation in neutrophils. We hypothesized that eCIRP induces MET formation by activating GSDMD. Human monocytic cell line THP-1 cells were differentiated with phorbol 12-myristate 13-acetate (PMA) and treated with recombinant murine (rm) CIRP. The MET formation was detected by three methods: time-lapse fluorescence microscopy (video imaging), colorimetry, and ELISA. Cleaved forms of GSDMD, and caspase-1 were detected by Western blotting. Treatment of THP-1 cells with rmCIRP increased MET formation as revealed by SYTOX Orange Staining assay in a time- and dose-dependent manner. METs formed by rmCIRP stimulation were further confirmed by extracellular DNA, citrullinated histone H3, and myeloperoxidase. Treatment of THP-1 cells with rmCIRP significantly increased the cleaved forms of caspase-1 and GSDMD compared to PBS-treated cells. Treatment of macrophages with caspase-1, and GSDMD inhibitors z-VAD-fmk, and disulfiram, separately, significantly decreased rmCIRP-induced MET formation. We also confirmed rmCIRP-induced MET formation using primary cells murine peritoneal macrophages. These data clearly show that eCIRP serves as a novel inducer of MET formation through the activation of GSDMD and caspase-1.

scholarly journals P149Angiotensin-II enhances neutrophil extracellular trap formation in an AT1R and NADPH oxidase-dependent manner

2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S39-S39 ◽  
Author(s):  
T M Hofbauer ◽  
T Scherz ◽  
A Ondracek ◽  
J Mueller ◽  
A Mangold ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Neutrophil Extracellular Trap ◽  
Dependent Manner ◽  
Trap Formation ◽  
Extracellular Trap

scholarly journals The Effects of Apigenin-Biosynthesized Ultra-Small Platinum Nanoparticles on the Human Monocytic THP-1 Cell Line

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 444 ◽  
Author(s):  
Sangiliyandi Gurunathan ◽  
Muniyandi Jeyaraj ◽  
Min-Hee Kang ◽  
Jin-Hoi Kim
Keyword(s):  
Cell Line ◽  
Chemical Properties ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Human Monocytic Cell Line ◽  
Physico Chemical ◽  
Proinflammatory Responses ◽  
Human Monocytic Cell ◽  
Dose Dependent

Generally, platinum nanoparticles (PtNPs) are considered non-toxic; however, toxicity depends on the size, dose, and physico-chemical properties of materials. Owing to unique physico-chemical properties, PtNPs have emerged as a material of interest for several biomedical applications, particularly therapeutics. The adverse effect of PtNPs on the human monocytic cell line (THP-1) is not well-established and remains elusive. Exposure to PtNPs may trigger oxidative stress and eventually lead to inflammation. To further understand the toxicological properties of PtNPs, we studied the effect of biologically synthesized ultra-small PtNPs on cytotoxicity, genotoxicity, and proinflammatory responses in the human monocytic cell line (THP-1). Our observations clearly indicated that PtNPs induce cytotoxicity in a dose-dependent manner by reducing cell viability and proliferation. The cytotoxicity of THP-1 cells correlated with an increase in the leakage of lactate dehydrogenase, generation of reactive oxygen species, and production of malondialdehyde, nitric oxide, and carbonylated proteins. The involvement of mitochondria in cytotoxicity and genotoxicity was confirmed by loss of mitochondrial membrane potential, lower ATP level, and upregulation of proapoptotic and downregulation of antiapoptotic genes. Decreases in the levels of antioxidants such as reduced glutathione (GSH), oxidized glutathione (GSH: GSSG), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and thioredoxin (TRX) were indicative of oxidative stress. Apoptosis was confirmed with the significant upregulation of key apoptosis-regulating genes. Oxidative DNA damage was confirmed by the increase in the levels of 8-oxodG and 8-oxoG and upregulation of DNA damage and repair genes. Finally, the proinflammatory responses to PtNPs was determined by assessing the levels of multiple cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1). All the cytokines were significantly upregulated in a dose-dependent manner. Collectively, these observations suggest that THP-1 cells were vulnerable to biologically synthesized ultra-small PtNPs.

scholarly journals Lipopolysaccharide Activates Caspase-1 (Interleukin-1–Converting Enzyme) in Cultured Monocytic and Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 577-584 ◽  
Author(s):  
Ralf R. Schumann ◽  
Claus Belka ◽  
Dirk Reuter ◽  
Norbert Lamping ◽  
Carsten J. Kirschning ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Cysteine Proteases ◽  
Precursor Protein ◽  
Converting Enzyme ◽  
Blood Monocytes ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Caspase 1

Abstract Interleukin-1β (IL-1β) is a pleiotropic proinflammatory cytokine. Mechanisms leading to its secretion include not only release of newly synthesized protein, but also cleavage of a preformed immature precursor protein into an active secretory form by the intracellular protease caspase-1 (formerly termed IL-1–converting enzyme [ICE]). Caspase-1 belongs to a rapidly growing family of cysteine proteases with substrate specificity for aspartate involved in cellular apoptosis. We have used an assay determining the caspase-1 activity based on cleavage of a fluorogenic peptide substrate to elucidate its role in lipopolysaccharide (LPS)-induced secretion of IL-1β. We show that LPS induces moderate caspase-1 activity in the monocytic cell line THP-1, in freshly isolated peripheral blood monocytes, and in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent fashion. Caspase-1 activation by LPS was associated with cleavage of the IL-1β precursor protein that was followed by release of the mature IL-1β protein in monocytic cells. In contrast, subsequent release of IL-1β by HUVECs was not significant. LPS-induced caspase-1 activation appeared not to result from modulation of caspase-1 transcript accumulation and inhibition of caspase-1 activity was accomplished by two specific inhibitors, YVAD-CHO and YVAD-CMK, capable of alleviating the release of mature IL-1β. Taken together, these results show that LPS moderately activates caspase-1 and that caspase-1 activation contributes to LPS induction of IL-1β secretion.

scholarly journals Neutrophil-Extracellular Traps, Cell-Free DNA, and Immunothrombosis in Companion Animals: A Review

2019 ◽  
Vol 57 (1) ◽  
pp. 6-23 ◽  
Author(s):  
Robert Goggs ◽  
Unity Jeffery ◽  
Dana N. LeVine ◽  
Ronald H. L. Li
Keyword(s):  
Companion Animals ◽  
High Mobility ◽  
Extracellular Dna ◽  
Death Process ◽  
Cell Free Dna ◽  
Pathogen Invasion ◽  
Extracellular Traps ◽  
Trap Formation ◽  
Free Dna ◽  
Extracellular Trap

Immunothrombosis is a potentially beneficial physiological process that aids innate immunity and host defense against pathogen invasion. However, this process can also be damaging when it occurs to excess or in critical blood vessels. Formation of extracellular traps by leukocytes, particularly neutrophils, is central to our understanding of immunothrombosis. In addition to degranulation and phagocytosis, extracellular traps are the third mechanism by which neutrophils combat potential pathogens. These traps consist of extracellular DNA decorated with bactericidal cellular proteins, including elastase, myeloperoxidase, and cathepsins. Neutrophils can release these structures as part of a controlled cell-death process or via a process termed vital NETosis that enables the cells to extrude DNA but remain viable. There is accumulating evidence that NETosis occurs in companion animals, including dogs, horses, and cats, and that it actively contributes to pathogenesis. Numerous studies have been published detailing various methods for identification and quantification of extracellular trap formation, including cell-free DNA, measurements of histones and proteins such as high-mobility group box–1, and techniques involving microscopy and flow cytometry. Here, we outline the present understanding of these phenomena and the mechanisms of extracellular trap formation. We critically review the data regarding measurement of NETosis in companion animals, summarize the existing literature on NETosis in veterinary species, and speculate on what therapeutic options these insights might present to clinicians in the future.

scholarly journals Lipoproteins from Staphylococcus aureus Drive Neutrophil Extracellular Trap Formation in a TLR2/1- and PAD-Dependent Manner

2021 ◽  
pp. ji2100283
Author(s):  
Jessica S. Hook ◽  
Parth A. Patel ◽  
Aidan O’Malley ◽  
Lihua Xie ◽  
Jeffrey S. Kavanaugh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Neutrophil Extracellular Trap ◽  
Dependent Manner ◽  
Trap Formation ◽  
Extracellular Trap

scholarly journals Neutrophil extracellular trap formation and extracellular DNA in sputum of stable COPD patients

2015 ◽  
Vol 109 (10) ◽  
pp. 1360-1362 ◽  
Author(s):  
Frauke Pedersen ◽  
Sebastian Marwitz ◽  
Olaf Holz ◽  
Anne Kirsten ◽  
Thomas Bahmer ◽  
...  
Keyword(s):  
Extracellular Dna ◽  
Neutrophil Extracellular Trap ◽  
Trap Formation ◽  
Copd Patients ◽  
Extracellular Trap

scholarly journals CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 1938-1947 ◽  
Author(s):  
Lamia Achour ◽  
Mark G. H. Scott ◽  
Hamasseh Shirvani ◽  
Alain Thuret ◽  
Georges Bismuth ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Dependent Manner ◽  
Small Interfering Rnas ◽  
Concentration Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Intracellular Compartments

The association of CD4, a glycoprotein involved in T-cell development and antigen recognition, and CC chemokine receptor 5 (CCR5), a chemotactic G protein–coupled receptor, which regulates trafficking and effector functions of immune cells, forms the main receptor for HIV. We observed that the majority of CCR5 is maintained within the intracellular compartments of primary T lymphocytes and in a monocytic cell line, contrasting with its relatively low density at the cell surface. The CCR5-CD4 association, which occurs in the endoplasmic reticulum, enhanced CCR5 export to the plasma membrane in a concentration-dependent manner, whereas inhibition of endogenous CD4 with small interfering RNAs decreased cell-surface expression of endogenous CCR5. This effect was specific for CCR5, as CD4 did not affect cellular distribution of CXCR4, the other HIV coreceptor. These results reveal a previously unappreciated role of CD4, which contributes to regulating CCR5 export to the plasma membrane.

Anti-Inflammatory Effect of Resveratrol by Inhibition of IL-8 Production in LPS-Induced THP-1 Cells

2009 ◽  
Vol 37 (06) ◽  
pp. 1203-1214 ◽  
Author(s):  
You-Chang Oh ◽  
Ok-Hwa Kang ◽  
Jang-Gi Choi ◽  
Hee-Sung Chae ◽  
Young-Seob Lee ◽  
...  
Keyword(s):  
Cell Activation ◽  
Inflammatory Diseases ◽  
Biological Effects ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Mapk Phosphorylation ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Iκbα Degradation

Resveratrol is a polyphenol compound and prominent anti-inflammatory agent found in plants, including the fruits of Morus alba. However, the therapeutic mechanisms of resveratrol remain largely unclear. To gain insight into the biological effects of resveratrol, we examined its influence on LPS-induced IL-8 production in the human monocytic cell line, THP-1. In inflammatory diseases, IL-8 plays a central role in the initiation and maintenance of inflammatory response. In the present study, IL-8 production was measured by ELISA and RT-PCR, while MAPK activation, IκBα degradation, nuclear factor (NF)-κB activation and cyclooxygenase (COX)-2 expression were determined by Western blot analysis. Resveratrol inhibited LPS-induced IL-8 production in a dose-dependent manner. Furthermore, resveratrol inhibited extracellular signal-regulated kinase (ERK) and p38 MAPK phosphorylation, IκBα degradation, NF-κB activation and cyclooxygenase (COX)-2 expression, which suggest that resveratrol inhibits IL-8 secretion by blocking MAPK phosphorylation and NF-κB activation. Taken together, these findings may help elucidate the mechanism by which resveratrol modulates THP-1 cell activation under inflammatory conditions.

scholarly journals Interferon-gamma upregulates interleukin-8 gene expression in human monocytic cells by a posttranscriptional mechanism

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 537-542
Author(s):  
MC Bosco ◽  
GL Gusella ◽  
I Espinoza-Delgado ◽  
DL Longo ◽  
L Varesio
Keyword(s):  
Gene Expression ◽  
Interferon Gamma ◽  
Mononuclear Phagocytes ◽  
Interleukin 8 ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Monocytic Cells ◽  
Ifn Gamma ◽  
Potent Inducer

Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is produced in response to several stimuli. Because monocytic cells are important producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent inducer of activation and differentiation of mononuclear phagocytes, affected IL-8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA expression that was upregulated by IFN-gamma in a dose- and time- dependent manner and via a protein-synthesis-dependent process in the human monocytic cell line U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on experiments showed that the IL- 8 gene was transcriptionally active in control cells and that IFN-gamma did not enhance the transcriptional activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the mRNA and, therefore, controlled primarily at a posttranscriptional level. These results represent the first evidence that IFN-gamma upregulates IL-8 gene expression in cells of the monocytic lineage, and show the involvement of posttranscriptional mechanisms in the induction of IL-8 mRNA.

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