Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults

Micah J. Drummond, Kyle L. Timmerman, Melissa M. Markofski, Dillon K. Walker, Jared M. Dickinson, Mohammad Jamaluddin, Allan R. Brasier, Blake Rasmussen, Elena Volpi

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and proinflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ~4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest (P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest (P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume305
Issue number3
DOIs
StatePublished - Aug 1 2013

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Bed Rest
Toll-Like Receptor 4
Interleukin-6
Skeletal Muscle
Cytokines
Inflammation
Muscles
Biopsy
Leg
CCAAT-Enhancer-Binding Protein-beta
Macrophage Inflammatory Proteins
Interleukin-15
Messenger RNA
Muscular Atrophy
Quadriceps Muscle
Serum
Interleukin-10
Interferons
Proteins
Anti-Inflammatory Agents

Keywords

  • Aging
  • Atrophy
  • Cytokine
  • Hospitalization
  • Physical inactivity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults. / Drummond, Micah J.; Timmerman, Kyle L.; Markofski, Melissa M.; Walker, Dillon K.; Dickinson, Jared M.; Jamaluddin, Mohammad; Brasier, Allan R.; Rasmussen, Blake; Volpi, Elena.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 305, No. 3, 01.08.2013.

Research output: Contribution to journalArticle

Drummond, Micah J. ; Timmerman, Kyle L. ; Markofski, Melissa M. ; Walker, Dillon K. ; Dickinson, Jared M. ; Jamaluddin, Mohammad ; Brasier, Allan R. ; Rasmussen, Blake ; Volpi, Elena. / Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2013 ; Vol. 305, No. 3.
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