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A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus
INTRODUCTION: The translocation of organismal molecules from gut into blood circulation might worsen the disease severity of lupus through the induction of neutrophil extracellular traps (NETs). METHODS: An impact of lipopolysaccharide (LPS) and (1→3)-β-D-glucan (BG), components of gut bacteria and...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179808/ https://www.ncbi.nlm.nih.gov/pubmed/34103965 http://dx.doi.org/10.2147/JIR.S305225 |
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author | Saithong, Supichcha Saisorn, Wilasinee Visitchanakun, Peerapat Sae-khow, Kritsanawan Chiewchengchol, Direkrit Leelahavanichkul, Asada |
author_facet | Saithong, Supichcha Saisorn, Wilasinee Visitchanakun, Peerapat Sae-khow, Kritsanawan Chiewchengchol, Direkrit Leelahavanichkul, Asada |
author_sort | Saithong, Supichcha |
collection | PubMed |
description | INTRODUCTION: The translocation of organismal molecules from gut into blood circulation might worsen the disease severity of lupus through the induction of neutrophil extracellular traps (NETs). METHODS: An impact of lipopolysaccharide (LPS) and (1→3)-β-D-glucan (BG), components of gut bacteria and fungi, respectively, on NETs formation, was explored in lupus models, Fc gamma receptor IIB deficiency (FcGRIIB-/-) and Pristane injection, using Candida-administered dextran sulfate solution induced colitis (Candida-DSS) model. RESULTS: Severity of Candida-DSS in FcGRIIB-/- mice was more prominent than wild-type (WT) and Pristane mice as indicated by (i) colonic NETs using immunofluorescence of Ly6G, myeloperoxidase (MPO) and neutrophil elastase (NE) together with expression of PAD4 and IL-1β, (ii) colonic immunoglobulin (Ig) deposition (immunofluorescence), (iii) gut-leakage by FITC-dextran assay, endotoxemia and serum BG, (iv) systemic inflammation (neutrophilia, serum cytokines, serum dsDNA and anti-dsDNA) and (v) renal injury (proteinuria, glomerular NETs and Ig deposition). DISCUSSION: The formation of NETs in Candida-DSS mice was more severe than non-Candida-DSS mice and NETs in Candida-DSS were more profound in FcGRIIB-/- mice than Pristane mice. Prominent NETs in Candida-DSS FcGRIIB-/- mice might be due to the profound responses against LPS+BG in FcGRIIB-/- neutrophils compared with WT cells. These data implied an impact of the inhibitory FcGRIIB in NETs formation and an influence of gut fungi in lupus exacerbation. Hence, gut fungi in a DSS-induced gut-leakage lupus model enhanced colonic NETs that facilitated gut translocation of organismal molecules and synergistically exacerbated lupus activity. |
format | Online Article Text |
id | pubmed-8179808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-81798082021-06-07 A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus Saithong, Supichcha Saisorn, Wilasinee Visitchanakun, Peerapat Sae-khow, Kritsanawan Chiewchengchol, Direkrit Leelahavanichkul, Asada J Inflamm Res Original Research INTRODUCTION: The translocation of organismal molecules from gut into blood circulation might worsen the disease severity of lupus through the induction of neutrophil extracellular traps (NETs). METHODS: An impact of lipopolysaccharide (LPS) and (1→3)-β-D-glucan (BG), components of gut bacteria and fungi, respectively, on NETs formation, was explored in lupus models, Fc gamma receptor IIB deficiency (FcGRIIB-/-) and Pristane injection, using Candida-administered dextran sulfate solution induced colitis (Candida-DSS) model. RESULTS: Severity of Candida-DSS in FcGRIIB-/- mice was more prominent than wild-type (WT) and Pristane mice as indicated by (i) colonic NETs using immunofluorescence of Ly6G, myeloperoxidase (MPO) and neutrophil elastase (NE) together with expression of PAD4 and IL-1β, (ii) colonic immunoglobulin (Ig) deposition (immunofluorescence), (iii) gut-leakage by FITC-dextran assay, endotoxemia and serum BG, (iv) systemic inflammation (neutrophilia, serum cytokines, serum dsDNA and anti-dsDNA) and (v) renal injury (proteinuria, glomerular NETs and Ig deposition). DISCUSSION: The formation of NETs in Candida-DSS mice was more severe than non-Candida-DSS mice and NETs in Candida-DSS were more profound in FcGRIIB-/- mice than Pristane mice. Prominent NETs in Candida-DSS FcGRIIB-/- mice might be due to the profound responses against LPS+BG in FcGRIIB-/- neutrophils compared with WT cells. These data implied an impact of the inhibitory FcGRIIB in NETs formation and an influence of gut fungi in lupus exacerbation. Hence, gut fungi in a DSS-induced gut-leakage lupus model enhanced colonic NETs that facilitated gut translocation of organismal molecules and synergistically exacerbated lupus activity. Dove 2021-06-01 /pmc/articles/PMC8179808/ /pubmed/34103965 http://dx.doi.org/10.2147/JIR.S305225 Text en © 2021 Saithong et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Saithong, Supichcha Saisorn, Wilasinee Visitchanakun, Peerapat Sae-khow, Kritsanawan Chiewchengchol, Direkrit Leelahavanichkul, Asada A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus |
title | A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus |
title_full | A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus |
title_fullStr | A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus |
title_full_unstemmed | A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus |
title_short | A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in Candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus |
title_sort | synergy between endotoxin and (1→3)-beta-d-glucan enhanced neutrophil extracellular traps in candida administered dextran sulfate solution induced colitis in fcgriib-/- lupus mice, an impact of intestinal fungi in lupus |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179808/ https://www.ncbi.nlm.nih.gov/pubmed/34103965 http://dx.doi.org/10.2147/JIR.S305225 |
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