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MMP-8 Genotypes Influence the Inflammatory Response in Human Endotoxemia
Clinical studies have reported associations between MMP-8 genotypes and clinical outcomes without exploring underlying mechanisms. This study aims to understand the influence of the rs1940475 SNP on downstream chemokine and cytokine response in human endotoxemia. Rs1940475 was genotyped in 44 health...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101851/ https://www.ncbi.nlm.nih.gov/pubmed/24170307 http://dx.doi.org/10.1007/s10753-013-9758-0 |
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author | Rella, Judith M. Jilma, Bernd Fabry, Astrid Kaynar, A. Murat Mayr, Florian B. |
author_facet | Rella, Judith M. Jilma, Bernd Fabry, Astrid Kaynar, A. Murat Mayr, Florian B. |
author_sort | Rella, Judith M. |
collection | PubMed |
description | Clinical studies have reported associations between MMP-8 genotypes and clinical outcomes without exploring underlying mechanisms. This study aims to understand the influence of the rs1940475 SNP on downstream chemokine and cytokine response in human endotoxemia. Rs1940475 was genotyped in 44 healthy Caucasian males, who were challenged with an intravenous bolus of 2 ng/kg lipopolysaccharide (LPS). Plasma levels of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were measured at baseline and 2, 4, 6, and 24 h after LPS infusion with high-sensitivity enzyme immunoassays. Peak TNF levels at 2 h after LPS infusion were significantly higher in subjects with AA genotype compared to subjects with AG or GG genotypes (185 pg/mL [IQR, 154–234] vs. 94 pg/mL [IQR, 65–125] vs. 107 pg/mL [IQR, 80–241], respectively; p = 0.03 between groups). Peak IL-6 levels were trend-wise higher in subjects with AA genotype compared to those with AG or GG genotypes (566 pg/mL [IQR, 294–644] vs. 278 pg/mL [IQR, 184–539] and 329 pg/mL [IQR, 240–492], respectively; p = 0.15 between groups). In contrast, peak MIP-1α at 2 h was highest in GG genotype carriers compared to those with AG or AA genotypes (602 pg/mL [IQR, 449–727] vs. 389 pg/mL [IQR, 375–490] and 510 pg/mL [425–813], respectively; p < 0.03 between groups). AA genotype carriers had highest peak TNF and IL-6 levels after LPS challenge, whereas peak MIP-1α levels were highest in GG carriers. This indicates that the rs1940475 SNP modifies the host response to inflammatory stimuli, which may in part explain previously shown associations with clinical outcomes. |
format | Online Article Text |
id | pubmed-7101851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-71018512020-03-31 MMP-8 Genotypes Influence the Inflammatory Response in Human Endotoxemia Rella, Judith M. Jilma, Bernd Fabry, Astrid Kaynar, A. Murat Mayr, Florian B. Inflammation Article Clinical studies have reported associations between MMP-8 genotypes and clinical outcomes without exploring underlying mechanisms. This study aims to understand the influence of the rs1940475 SNP on downstream chemokine and cytokine response in human endotoxemia. Rs1940475 was genotyped in 44 healthy Caucasian males, who were challenged with an intravenous bolus of 2 ng/kg lipopolysaccharide (LPS). Plasma levels of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were measured at baseline and 2, 4, 6, and 24 h after LPS infusion with high-sensitivity enzyme immunoassays. Peak TNF levels at 2 h after LPS infusion were significantly higher in subjects with AA genotype compared to subjects with AG or GG genotypes (185 pg/mL [IQR, 154–234] vs. 94 pg/mL [IQR, 65–125] vs. 107 pg/mL [IQR, 80–241], respectively; p = 0.03 between groups). Peak IL-6 levels were trend-wise higher in subjects with AA genotype compared to those with AG or GG genotypes (566 pg/mL [IQR, 294–644] vs. 278 pg/mL [IQR, 184–539] and 329 pg/mL [IQR, 240–492], respectively; p = 0.15 between groups). In contrast, peak MIP-1α at 2 h was highest in GG genotype carriers compared to those with AG or AA genotypes (602 pg/mL [IQR, 449–727] vs. 389 pg/mL [IQR, 375–490] and 510 pg/mL [425–813], respectively; p < 0.03 between groups). AA genotype carriers had highest peak TNF and IL-6 levels after LPS challenge, whereas peak MIP-1α levels were highest in GG carriers. This indicates that the rs1940475 SNP modifies the host response to inflammatory stimuli, which may in part explain previously shown associations with clinical outcomes. Springer US 2013-10-30 2014 /pmc/articles/PMC7101851/ /pubmed/24170307 http://dx.doi.org/10.1007/s10753-013-9758-0 Text en © Springer Science+Business Media New York 2013 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Article Rella, Judith M. Jilma, Bernd Fabry, Astrid Kaynar, A. Murat Mayr, Florian B. MMP-8 Genotypes Influence the Inflammatory Response in Human Endotoxemia |
title | MMP-8 Genotypes Influence the Inflammatory Response in Human Endotoxemia |
title_full | MMP-8 Genotypes Influence the Inflammatory Response in Human Endotoxemia |
title_fullStr | MMP-8 Genotypes Influence the Inflammatory Response in Human Endotoxemia |
title_full_unstemmed | MMP-8 Genotypes Influence the Inflammatory Response in Human Endotoxemia |
title_short | MMP-8 Genotypes Influence the Inflammatory Response in Human Endotoxemia |
title_sort | mmp-8 genotypes influence the inflammatory response in human endotoxemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101851/ https://www.ncbi.nlm.nih.gov/pubmed/24170307 http://dx.doi.org/10.1007/s10753-013-9758-0 |
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