Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.

<h4>Background</h4>The regulation of muscle stem cells in humans in response to muscle injury remains largely undefined. Recently, interleukin-6 (IL-6) has been implicated in muscle stem cell (satellite cell)-mediated muscle hypertrophy in animals; however, the role of IL-6 in the satell...

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Autores principales:	Bryon R McKay, Michael De Lisio, Adam P W Johnston, Ciara E O'Reilly, Stuart M Phillips, Mark A Tarnopolsky, Gianni Parise
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bda8e7d07a284a7daef6c07bfde0ce07
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spelling	oai:doaj.org-article:bda8e7d07a284a7daef6c07bfde0ce072021-11-25T06:21:55ZAssociation of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.1932-620310.1371/journal.pone.0006027https://doaj.org/article/bda8e7d07a284a7daef6c07bfde0ce072009-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19554087/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The regulation of muscle stem cells in humans in response to muscle injury remains largely undefined. Recently, interleukin-6 (IL-6) has been implicated in muscle stem cell (satellite cell)-mediated muscle hypertrophy in animals; however, the role of IL-6 in the satellite cell (SC) response following muscle-lengthening contractions in humans has not been studied.<h4>Methodology/principal findings</h4>Eight subjects (age 22+/-1 y; 79+/-8 kg) performed 300 maximal unilateral lengthening contractions (3.14 rad.s(-1)) of the knee extensors. Blood and muscle samples were collected before and at 4, 24, 72, and 120 hours post intervention. IL-6, IL-6 receptor, IL-6R(alpha), cyclin D1, suppressor of cytokine signling-3 (SOCS3) mRNA were measured using quantitative RT-PCR and serum IL-6 protein was measured using an ELISA kit. JAK2 and STAT3 phosphorylated and total protein was measured using western blotting techniques. Immunohistochemical analysis of muscle cross-sections was performed for the quantification of SCs (Pax7(+) cells) as well as the expression of phosphorylated STAT3, IL-6, IL-6R(alpha), and PCNA across all time-points. The SC response, as defined by an amplification of Pax7(+) cells, was rapid, increasing by 24 h and peaking 72 h following the intervention. Muscle IL-6 mRNA increased following the intervention, which correlated strongly (R(2) = 0.89, p<0.002) with an increase in serum IL-6 concentration. SC IL-6R(alpha) protein was expressed on the fiber, but was also localized to the SC, and IL-6(+) SC increased rapidly following muscle-lengthening contractions and returned to basal levels by 72 h post-intervention, demonstrating an acute temporal expression of IL-6 with SC. Phosphorylated STAT3 was evident in SCs 4 h after lengthening contraction, and the downstream genes, cyclin D1 and SOCS3 were significantly elevated 24 hours after the intervention.<h4>Conclusions/significance</h4>The increased expression of STAT3 responsive genes and expression of IL-6 within SCs demonstrate that IL-6/STAT3 signaling occurred in SCs, correlating with an increase in SC proliferation, evidenced by increased Pax7(+)/PCNA(+) cell number in the early stages of the time-course. Collectively, these data illustrate that IL-6 is an important signaling molecule associated with the SC response to acute muscle-lengthening contractions in humans.Bryon R McKayMichael De LisioAdam P W JohnstonCiara E O'ReillyStuart M PhillipsMark A TarnopolskyGianni ParisePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 6, p e6027 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bryon R McKay Michael De Lisio Adam P W Johnston Ciara E O'Reilly Stuart M Phillips Mark A Tarnopolsky Gianni Parise Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.
description	<h4>Background</h4>The regulation of muscle stem cells in humans in response to muscle injury remains largely undefined. Recently, interleukin-6 (IL-6) has been implicated in muscle stem cell (satellite cell)-mediated muscle hypertrophy in animals; however, the role of IL-6 in the satellite cell (SC) response following muscle-lengthening contractions in humans has not been studied.<h4>Methodology/principal findings</h4>Eight subjects (age 22+/-1 y; 79+/-8 kg) performed 300 maximal unilateral lengthening contractions (3.14 rad.s(-1)) of the knee extensors. Blood and muscle samples were collected before and at 4, 24, 72, and 120 hours post intervention. IL-6, IL-6 receptor, IL-6R(alpha), cyclin D1, suppressor of cytokine signling-3 (SOCS3) mRNA were measured using quantitative RT-PCR and serum IL-6 protein was measured using an ELISA kit. JAK2 and STAT3 phosphorylated and total protein was measured using western blotting techniques. Immunohistochemical analysis of muscle cross-sections was performed for the quantification of SCs (Pax7(+) cells) as well as the expression of phosphorylated STAT3, IL-6, IL-6R(alpha), and PCNA across all time-points. The SC response, as defined by an amplification of Pax7(+) cells, was rapid, increasing by 24 h and peaking 72 h following the intervention. Muscle IL-6 mRNA increased following the intervention, which correlated strongly (R(2) = 0.89, p<0.002) with an increase in serum IL-6 concentration. SC IL-6R(alpha) protein was expressed on the fiber, but was also localized to the SC, and IL-6(+) SC increased rapidly following muscle-lengthening contractions and returned to basal levels by 72 h post-intervention, demonstrating an acute temporal expression of IL-6 with SC. Phosphorylated STAT3 was evident in SCs 4 h after lengthening contraction, and the downstream genes, cyclin D1 and SOCS3 were significantly elevated 24 hours after the intervention.<h4>Conclusions/significance</h4>The increased expression of STAT3 responsive genes and expression of IL-6 within SCs demonstrate that IL-6/STAT3 signaling occurred in SCs, correlating with an increase in SC proliferation, evidenced by increased Pax7(+)/PCNA(+) cell number in the early stages of the time-course. Collectively, these data illustrate that IL-6 is an important signaling molecule associated with the SC response to acute muscle-lengthening contractions in humans.
format	article
author	Bryon R McKay Michael De Lisio Adam P W Johnston Ciara E O'Reilly Stuart M Phillips Mark A Tarnopolsky Gianni Parise
author_facet	Bryon R McKay Michael De Lisio Adam P W Johnston Ciara E O'Reilly Stuart M Phillips Mark A Tarnopolsky Gianni Parise
author_sort	Bryon R McKay
title	Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.
title_short	Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.
title_full	Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.
title_fullStr	Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.
title_full_unstemmed	Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.
title_sort	association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/bda8e7d07a284a7daef6c07bfde0ce07
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Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.

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