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Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone
The abundance, anatomical distribution, and vascularity of skeletal muscle make it a potentially important contributor to local cytokine production and systemic cytokine abundance during inflammatory events. An orchestrated balance between the production of pro- and anti-inflammatory mediators is ne...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260049/ https://www.ncbi.nlm.nih.gov/pubmed/35814217 http://dx.doi.org/10.3389/fphar.2022.917917 |
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author | Bivona III, Joseph J. Mank, Madeleine M. Stapleton, Renee D. Files, D. Clark Toth, Michael J. Poynter, Matthew E. |
author_facet | Bivona III, Joseph J. Mank, Madeleine M. Stapleton, Renee D. Files, D. Clark Toth, Michael J. Poynter, Matthew E. |
author_sort | Bivona III, Joseph J. |
collection | PubMed |
description | The abundance, anatomical distribution, and vascularity of skeletal muscle make it a potentially important contributor to local cytokine production and systemic cytokine abundance during inflammatory events. An orchestrated balance between the production of pro- and anti-inflammatory mediators is necessary for proper immune function, yet the contribution of the body’s largest organ system, comprised primarily of skeletal muscle myocytes that fuse to form myofibers, to this process is largely unknown. Endotoxin (lipopolysaccharide, LPS) stimulates toll-like receptor 4 (TLR4) to induce the production of several pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2), by a of myriad cell types. We sought to quantify the influence of myofibers on systemic cytokine concentrations following an acute endotoxemia challenge. To accomplish this, we generated muscle specific conditional knockouts for TLR4 (TLR4SMKO), IL-6 (IL6SMKO), and CCL2 (CCL2SMKO). We administered low concentrations of intravenous LPS (IV LPS) to these receptor and effector knockout mice and collected samples after 3 h. Using gene expression analysis of gastrocnemius muscle and serum cytokine measurements after IV LPS, we determined that deletion of myofiber IL-6 or CCL2 led to a 93% and 57% reduction of these specific cytokines in the systemic circulation, respectively. Myofiber specific TLR4 deletion decreased the expression of IL-6, CCL2, and C-X-C motif chemokine ligand 1 (CXCL1) in the gastrocnemius muscle. These data indicate the critical involvement and direct contribution of myofibers during the early systemic inflammatory cytokine response to endotoxin. |
format | Online Article Text |
id | pubmed-9260049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92600492022-07-08 Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone Bivona III, Joseph J. Mank, Madeleine M. Stapleton, Renee D. Files, D. Clark Toth, Michael J. Poynter, Matthew E. Front Pharmacol Pharmacology The abundance, anatomical distribution, and vascularity of skeletal muscle make it a potentially important contributor to local cytokine production and systemic cytokine abundance during inflammatory events. An orchestrated balance between the production of pro- and anti-inflammatory mediators is necessary for proper immune function, yet the contribution of the body’s largest organ system, comprised primarily of skeletal muscle myocytes that fuse to form myofibers, to this process is largely unknown. Endotoxin (lipopolysaccharide, LPS) stimulates toll-like receptor 4 (TLR4) to induce the production of several pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2), by a of myriad cell types. We sought to quantify the influence of myofibers on systemic cytokine concentrations following an acute endotoxemia challenge. To accomplish this, we generated muscle specific conditional knockouts for TLR4 (TLR4SMKO), IL-6 (IL6SMKO), and CCL2 (CCL2SMKO). We administered low concentrations of intravenous LPS (IV LPS) to these receptor and effector knockout mice and collected samples after 3 h. Using gene expression analysis of gastrocnemius muscle and serum cytokine measurements after IV LPS, we determined that deletion of myofiber IL-6 or CCL2 led to a 93% and 57% reduction of these specific cytokines in the systemic circulation, respectively. Myofiber specific TLR4 deletion decreased the expression of IL-6, CCL2, and C-X-C motif chemokine ligand 1 (CXCL1) in the gastrocnemius muscle. These data indicate the critical involvement and direct contribution of myofibers during the early systemic inflammatory cytokine response to endotoxin. Frontiers Media S.A. 2022-06-23 /pmc/articles/PMC9260049/ /pubmed/35814217 http://dx.doi.org/10.3389/fphar.2022.917917 Text en Copyright © 2022 Bivona III, Mank, Stapleton, Files, Toth and Poynter. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Bivona III, Joseph J. Mank, Madeleine M. Stapleton, Renee D. Files, D. Clark Toth, Michael J. Poynter, Matthew E. Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone |
title | Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone |
title_full | Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone |
title_fullStr | Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone |
title_full_unstemmed | Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone |
title_short | Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone |
title_sort | skeletal muscle myofibers directly contribute to lps-induced systemic inflammatory tone |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260049/ https://www.ncbi.nlm.nih.gov/pubmed/35814217 http://dx.doi.org/10.3389/fphar.2022.917917 |
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