Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFα, in mice lacking interleukin-10

Huey, Kimberly A.; McCusker, Robert H.; Kelley, Keith W.

doi:10.1016/j.jneuroim.2008.05.004

Cited by 12 publications

(9 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The IL-10 results (Fig. 3) also support the IL-6 findings, as IL-6 infusion increases IL-10 in humans (53) and IL-10 knockout animals have an exaggerated skeletal muscle IL-6 response to an inflammatory insult (26), suggesting IL-10 is a regulator of IL-6.…”

Section: Discussionsupporting

confidence: 68%

Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults

Trappe

Standley

Jemioło

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Twelve weeks of resistance training (3 days/wk) combined with daily consumption of the cyclooxygenase-inhibiting drugs acetaminophen (4.0 g/day; n = 11, 64 ± 1 yr) or ibuprofen (1.2 g/day; n = 13, 64 ± 1 yr) unexpectedly promoted muscle mass and strength gains 25-50% above placebo (n = 12, 67 ± 2 yr). To investigate the mechanism of this adaptation, muscle biopsies obtained before and ∼72 h after the last training bout were analyzed for mRNA levels of prostaglandin (PG)/cyclooxygenase pathway enzymes and receptors [arachidonic acid synthesis: cytosolic phospholipase A(2) (cPLA(2)) and secreted phospholipase A(2) (sPLA(2)); PGF(2α) synthesis: PGF(2α) synthase and PGE(2) to PGF(2α) reductase; PGE(2) synthesis: PGE(2) synthase-1, -2, and -3; PGF(2α) receptor and PGE(2) receptor-4], cytokines and myokines involved in skeletal muscle adaptation (TNF-α, IL-1β, IL-6, IL-8, IL-10), and regulators of muscle growth [myogenin, myogenic regulatory factor-4 (MRF4), myostatin] and atrophy [Forkhead box O3A (FOXO3A), atrogin-1, muscle RING finger protein 1 (MuRF-1), inhibitory κB kinase β (IKKβ)]. Training increased (P < 0.05) cPLA(2), PGF(2α) synthase, PGE(2) to PGF(2α) reductase, PGE(2) receptor-4, TNF-α, IL-1β, IL-8, and IKKβ. However, the PGF(2α) receptor was upregulated (P < 0.05) only in the drug groups, and the placebo group upregulation (P < 0.05) of IL-6, IL-10, and MuRF-1 was eliminated in both drug groups. These results highlight prostaglandin and myokine involvement in the adaptive response to exercise in older individuals and suggest two mechanisms underlying the enhanced muscle mass gains in the drug groups: 1) The drug-induced PGF(2α) receptor upregulation helped offset the drug suppression of PGF(2α)-stimulated protein synthesis after each exercise bout and enhanced skeletal muscle sensitivity to this stimulation. 2) The drug-induced suppression of intramuscular PGE(2) production increased net muscle protein balance after each exercise bout through a reduction in PGE(2)-induced IL-6 and MuRF-1, both promoters of muscle loss.

show abstract

Section: Discussionsupporting

confidence: 68%

Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults

Trappe

Standley

Jemioło

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…We suspect that although this reduction is significant, the 100-fold increase in IL-6 mRNA seen in the tolerant mice approaches the maximal capacity of the cells to translate the protein. Further mRNA induction would not induce much more protein expression, accounting for the fact that a similar dramatic reduction in IL-6 protein was not observed (25). Additionally, the antiinflammatory mediator IL-10 has been shown to play a role in various models of LPS tolerance (26, 27).…”

Section: Resultsmentioning

confidence: 99%

Acute Pulmonary Lipopolysaccharide Tolerance Decreases TNF-α without Reducing Neutrophil Recruitment

Natarajan

Kim

Remick

2008

The Journal of Immunology

View full text Add to dashboard Cite

Pulmonary LPS exposure plays a key role in exacerbation of lung diseases such as chronic obstructive pulmonary disease and asthma. However, little is known about the effects of repeated LPS exposure in the lung microenvironment. We have developed a novel murine model of pulmonary LPS tolerance induced by intratracheal (i.t.) administration of LPS. First, we show that pulmonary LPS exposure does not induce whole-body refractoriness to systemic LPS, because i.t. administration followed by i.p. administration did not decrease plasma TNF-α. However, a local refractory state can be induced with two i.t. LPS exposures. Pulmonary LPS tolerance was induced by i.t. administration of 100 ng LPS at time 0 and 48 h. Nontolerant mice received PBS at time 0 and LPS at 48 h. Bronchoalveolar lavage levels of TNF-α were significantly attenuated in tolerant mice vs nontolerant mice (1597 pg/ml vs 7261 pg/ml). TNF-α mRNA was significantly reduced in bronchoalveolar lavage cells (5-fold) and lung tissue (10-fold). No reduction was seen in neutrophil numbers in the bronchoalveolar lavage fluid, myeloperoxidase activity, or expression of neutrophil chemoattractants CXCL1 and CXCL2, reflecting the specificity of the response. The reduction in TNF-α was accompanied by a significant increase in soluble receptors, TNF-SRI (159 pg/ml vs 206 pg/ml) and TNF-SRII (1366 pg/m vs 2695 pg/ml). In conclusion, pulmonary LPS tolerance results in a specific reduction in TNF-α expression, while the neutrophilic response is unaffected. This response may be a mechanism to limit tissue damage by reducing TNF-α levels, while still maintaining the antimicrobial capacity of the lung.

show abstract

“…IL-10 is well known for its function to suppress inflammatory immune responses by targeting the transcription of pro-inflammatory mediators (33). Since IL-10 mRNA was elevated with bed rest, it is possible that this might be a mechanism to counteract a pro-inflammatory response (21). In fact, IL-6 is known to stimulate IL-10 production, thereby providing a physiological brake on the overall pro-inflammatory status (45).…”

Section: Discussionmentioning

confidence: 99%

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

Drummond

Timmerman

Markofski³

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

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 pro-inflammatory 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.

show abstract

Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFα, in mice lacking interleukin-10

Cited by 12 publications

References 38 publications

Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults

Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults

Acute Pulmonary Lipopolysaccharide Tolerance Decreases TNF-α without Reducing Neutrophil Recruitment

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

Contact Info

Product

Resources

About