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Journal ArticleDOI

Skeletal muscle IL-15/IL-15Rα and myofibrillar protein synthesis after resistance exercise.

01 Jan 2018-Scandinavian Journal of Medicine & Science in Sports (Scand J Med Sci Sports)-Vol. 28, Iss: 1, pp 116-125

TL;DR: In conclusion, IL‐15/IL‐15Rα signaling pathway is activated in skeletal muscle in response to a session of resistance exercise.

AbstractIn vitro and in vivo studies described the myokine IL-15 and its receptor IL-15Rα as anabolic/anti-atrophy agents, however, the protein expression of IL-15Rα has not been measured in human skeletal muscle and data regarding IL-15 expression remain inconclusive. The purpose of the study was to determine serum and skeletal muscle IL-15 and IL-15Rα responses to resistance exercise session and to analyze their association with myofibrillar protein synthesis (MPS). Fourteen participants performed a bilateral leg resistance exercise composed of four sets of leg press and four sets of knee extension at 75% 1RM to task failure. Muscle biopsies were obtained at rest, 0, 4 and 24 hours post-exercise and blood samples at rest, mid-exercise, 0, 0.3, 1, 2, 4 and 24 hours post-exercise. Serum IL-15 was increased by ~5.3-fold immediately post-exercise, while serum IL-15Rα decreased ~75% over 1 hour post-exercise (P<.001). Skeletal muscle IL-15Rα mRNA and protein expression were increased at 4 hours post-exercise by ~2-fold (P<.001) and ~1.3-fold above rest (P=.020), respectively. At 24 hours post-exercise, IL-15 (P=.003) and IL-15Rα mRNAs increased by ~2-fold (P=.002). Myofibrillar fractional synthetic rate between 0-4 hours was associated with IL-15Rα mRNA at rest (r=.662, P=.019), 4 hours (r=.612, P=.029), and 24 hours post-exercise (r=.627, P=.029). Finally, the muscle IL-15Rα protein up-regulation was related to Leg press 1RM (r=.688, P=.003) and total weight lifted (r=.628, P=.009). In conclusion, IL-15/IL-15Rα signaling pathway is activated in skeletal muscle in response to a session of resistance exercise.

Topics: Skeletal muscle (61%), Leg press (54%), Myokine (53%), Myofibril (51%)

Summary (2 min read)

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  • IL-15Rα has not been determined in human skeletal muscle.
  • Therefore, despite the 67 fact that in vitro studies indicate a role for skeletal muscle IL-15 in anabolism, studies in 68 humans are inconclusive.
  • Of 119 the 16 participants included in the original study, 14 were analysed in the present investigation 120 due to insufficient muscle tissue in the two subjects excluded.

Experimental protocol 123

  • A detailed description of the experimental protocol and analytical methods can be found 124 elsewhere (McKendry et al., 2016) .
  • Thereafter, one-repetition maximum (1RM) strength during leg press and 127 knee extension was assessed (Cybex VR-3, MA, USA).
  • The following morning at 7.00 h, participants returned to the 142 laboratory after a 10-12h overnight fast and a cannula was inserted into a forearm vein to obtain 143 a blood sample followed by the fourth and last biopsy, which was obtained from the vastus 144 lateralis of the contralateral leg.
  • The participants received three standardised meals for consumption the evening prior to 147 the experimental trial, as well as the afternoon and evening after the experimental trial.

Serum IL-15 and IL-15Rα 154

  • After collection, all blood samples were centrifuged for 15 minutes at 1000 g, aliquoted and 155 stored at -80 ºC.
  • Two high-sensitivity enzyme-linked immunosorbent assay kits were 156 used to determine the serum concentration of IL-15 and IL-15Rα in duplicates.

Both antibodies were diluted into BSA-blocking buffer containing 4% bovine serum albumin in 175

  • Antibody specific labelling was revealed by 176 incubation with an HRP-conjugated goat anti-rabbit (IL-15) or anti-mouse (IL-15Rα) antibodies 177 (1:5000), both diluted in 5% blotto blocking buffer and visualised with ECL Western blotting 178 detection system using a ChemiDoc XRS (Bio-Rad, Copenhagen, Denmark).
  • Imaging and band 179 quantification were performed using the Quantity One 1-D Analysis software (Bio-Rad, 180 Copenhagen, Denmark).
  • Test samples were run together with a control sample from a subject 181 who did not take part in the study.
  • The control sample was loaded in three different lanes and 182 used as an internal control for inter-gel variability.

RNA Isolation and quantitative real-time reverse transcription polymerase chain reaction 187 (qRT-PCR). 188

  • Approximately 15-20 mg of skeletal muscle tissue was used for the RNA isolation.
  • The RNA 189 was extracted by guanine-phenol-chloroform isothiocyanate procedures using TRIzol 190 (AUC) was determined using trapezoid method and compared between groups using a paired 242 Student's t-test.
  • Since no significant differences were observed between the 1-and 5-min 243 recovery, both groups were combined for further analyses.
  • To determine time effects of the intervention on serum, protein and mRNA levels of IL-245 15 and IL-15Rα, ANOVA for repeated measures was performed.
  • Tukey HSD correction was 246 used as post-hoc test when significant differences were detected.

Skeletal muscle IL-15/IL-15Rα expression and myofibrillar protein synthesis. 306

  • This lack of 328 differences could be interpreted as evidence to refute the association between skeletal muscle 329 IL-15/IL-15Rα and MPS.
  • Nevertheless, the effect sizes and statistical outputs (P<0.10) indicate 330 that a potential difference between groups may actually exist.
  • In agreement, the authors have observed a positive association between serum concentration of 395 IL-15 and IL-15 protein levels in skeletal muscle, suggesting that muscle may be an important 396 source of IL-15 in the basal state.
  • In the present study, the authors observed that basal IL-15 protein 397 levels in skeletal muscle were associated with serum concentration immediately post-exercise, 398 also suggesting that the size of the intramuscular pool could determine the magnitude of the 399 increase in serum IL-15 elicited by resistance exercise.

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University of Birmingham
Skeletal muscle IL-15/IL-15R and myofibrillar protein
synthesis after resistance exercise
Pérez López, Alberto; McKendry, James; Martin-Rincon, Marcos ; Morales-Alamo, David;
Pérez-Köhler, Bárbara ; Valadés, David; Buján, Julia ; Calbet, Jose; Breen, Leigh
DOI:
10.1111/sms.12901
License:
None: All rights reserved
Document Version
Peer reviewed version
Citation for published version (Harvard):
Pérez López, A, McKendry, J, Martin-Rincon, M, Morales-Alamo, D, Pérez-Köhler, B, Valadés, D, Buján, J,
Calbet, J & Breen, L 2017, 'Skeletal muscle IL-15/IL-15R and myofibrillar protein synthesis after resistance
exercise', Scandinavian Journal of Medicine and Science in Sports. https://doi.org/10.1111/sms.12901
Link to publication on Research at Birmingham portal
Publisher Rights Statement:
Checked for eligibility: 27/04/2017
"This is the peer reviewed version of the following article: Pérez-López A, McKendry J, Martin-Rincon M, et al. Skeletal muscle IL-15/IL-15R
and myofibrillar protein synthesis after resistance exercise. Scand J Med Sci Sports. 2017, which has been published in final form at
https://doi.org/10.1111/sms.12901. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions
for Self-Archiving."
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Download date: 09. Aug. 2022

PROOF
Skeletal muscle IL
-
15
/IL
-
synthesis after resistance exercise
Journal:
Scandinavian Journal of Medicine and Science in Sports
Manuscript ID
SJMSS-O-694-16.R2
Manuscript Type:
Original Article
Date Submitted by the Author:
27-Mar-2017
Complete List of Authors:
Pérez-López, Alberto; University of Alcalá, Medicine and Medical
Specialties. Faculty of Medicine and Health Sciences. Biomedical Research
Networking Centre on Bioengineering, Biomaterials and Nanomedicine
(CIBER-BBN); University of Alcalá, Biomedical Sciences. Faculty of
Medicine and Health Sciences; University of Birmingham, School of Sport,
Exercise and Rehabilitation Sciences; University of Las Palmas de Gran
Canaria, Department of Physical Education. Faculty of Physical Education
McKendry, James; University of Birmingham, School of Sport, Exercise and
Rehabilitation Sciences; University of Birmingham, MRC-ARUK Centre for
Musculoskeletal Ageing Research
Martin-Rincon, Marcos; University of Las Palmas de Gran Canaria,
Department of Physical Education. Faculty of Physical Education; University
of Las Palmas de Gran Canaria, Research Institute of Biomedical and
Health Sciences (IUIBS)
Morales-Alamo, David; University of Las Palmas de Gran Canaria,
Department of Physical Education. Faculty of Physical Education; University
of Las Palmas de Gran Canaria, Research Institute of Biomedical and
Health Sciences (IUIBS)
Pérez-Köhler, Bárbara; University of Alcalá, Department of Medicine and
Medical Specialities. Faculty of Medicine and Health Sciences. Biomedical
Research Networking Centre on Bioengineering, Biomaterials and
Nanomedicine (CIBER-BBN)
Valadés, David; University of Alcalá, Department of Biomedical Sciences.
Faculty of Medicine and Health Sciences.
Buján, Julia; University of Alcalá, Department of Medicine and Medical
Specialities. Faculty of Medicine and Health Sciences. Biomedical Research
Networking Centre on Bioengineering, Biomaterials and Nanomedicine
(CIBER-BBN)
Calbet, Jose; University of Las Palmas de Gran Canaria, Department of
Physical Education. Faculty of Physical Education; University of Las Palmas
de Gran Canaria, Research Institute of Biomedical and Health Sciences
(IUIBS)
Breen, Leigh; University of Birmingham, School of Sport, Exercise and
Rehabilitation Sciences; University of Birmingham, MRC-ARUK Centre for
Musculoskeletal Ageing Research
Keywords:
Myokines, IL-15/IL-15Rα axis, strength training, muscle protein
synthesis/breakdown
Scandinavian Journal of Medicine & Science in Sports - PROOF
Scandinavian Journal of Medicine & Science in Sports - PROOF

PROOF
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PROOF
1
Skeletal muscle IL-15/IL-15Rα and myofibrillar protein synthesis after resistance 1
exercise 2
3
Alberto Pérez-López
1,2,3,4
, James McKendry
3,5
, Marcos Martin-Rincon
4,6
, David Morales-4
Alamo
4,6
, Bárbara Pérez-Köhler
1
, David Valadés
2
, Julia Buján
1
, Jose A. L. Calbet
4,6
and 5
Leigh Breen
3,5
.6
7
1
Department of Medicine and Medical Specialities. Faculty of Medicine and Health Sciences. 8
University of Alcalá, Madrid, Spain. Biomedical Research Networking Centre on 9
Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. 10
2
Department of Biomedical Sciences. Faculty of Medicine and Health Sciences. University of 11
Alcalá, Madrid, Spain. 12
3
School of Sport, Exercise and Rehabilitation Sciences. University of Birmingham, 13
Birmingham, UK. 14
4
Department of Physical Education. Faculty of Physical Education. University of Las Palmas 15
de Gran Canaria, Las Palmas de Gran Canaria, Spain. 16
5
MRC-ARUK Centre for Musculoskeletal Ageing Research. University of Birmingham, 17
Birmingham, UK. 18
6
Research Institute of Biomedical and Health Sciences (IUIBS). Las Palmas de Gran Canaria, 19
Spain. 20
21
Address for correspondence: 22
Alberto Pérez-López 23
Department of Medicine and Medical Specialties. 24
Faculty of Medicine and Health Sciences, University of Alcalá. 25
Ctra. Madrid-Barcelona km 33,600 26
28871 Alcalá de Henares, Madrid (Spain) 27
E-mail: Alberto_perez-lopez@hotmail.com
28
Phone: (+34) 636 710 130 29
30
Running head: IL-15/IL-15Rα in Resistance Exercise
31
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PROOF
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ABSTRACT 32
In vitro and in vivo studies described the myokine IL-15 and its receptor IL-15Rα as 33
anabolic/anti-atrophy agents, however the protein expression of IL-15Rα has not been measured 34
in human skeletal muscle and data regarding IL-15 expression remain inconclusive. The 35
purpose of the study was to determine serum and skeletal muscle IL-15 and IL-15Rα responses 36
to resistance exercise session and to analyse their association with myofibrillar protein synthesis 37
(MPS). Fourteen participants performed a bilateral leg resistance exercise composed of 4 sets of 38
leg press and 4 sets of knee extension at 75% 1RM to task failure. Muscle biopsies were 39
obtained at rest, 0, 4 and 24h post-exercise and blood samples at rest, mid-exercise, 0, 0.3, 1, 2, 40
4 and 24h post-exercise. Serum IL-15 was increased by ~5.3-fold immediately post-exercise, 41
while serum IL-15Rα decreased ~75% over 1h post-exercise (P<0.001). Skeletal muscle IL-42
15Rα mRNA and protein expression were increased at 4h post-exercise by ~2-fold (P<0.001) 43
and ~1.3-fold above rest (P=0.020), respectively. At 24h post-exercise IL-15 (P=0.003) and IL-44
15Rα mRNAs increased by ~2-fold (P=0.002). Myofibrillar fractional synthetic rate between 0-45
4h was associated with IL-15Rα mRNA at rest (r=0.662, P=0.019), 4h (r=0.612, P=0.029) and 46
24h post-exercise (r=0.627, P=0.029). Finally, the muscle IL-15Rα protein up-regulation was 47
related to Leg press 1RM (r=0.688, P=0.003) and total weight lifted (r=0.628, P=0.009). In 48
conclusion, IL-15/IL-15Rα signalling pathway is activated in skeletal muscle in response to a 49
session of resistance exercise. 50
Keywords: Myokines, IL-15/IL-15Rα axis, strength training, muscle protein 51
synthesis/breakdown. 52
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TL;DR: A search found that a single session of endurance exercise at moderate or vigorous intensity stimulates an increase in the circulating levels of hepcidin between 0 h and 6 h after the end of the exercise bout, peaking at ~3 h post-exercise.
Abstract: Iron deficiency is a frequent and multifactorial disorder in the career of athletes, particularly in females. Exercise-induced disturbances in iron homeostasis produce deleterious effects on performance and adaptation to training; thus, the identification of strategies that restore or maintain iron homeostasis in athletes is required. Hepcidin is a liver-derived hormone that degrades the ferroportin transport channel, thus reducing the ability of macrophages to recycle damaged iron, and decreasing iron availability. Although it has been suggested that the circulating fraction of hepcidin increases during early post-exercise recovery (~3 h), it remains unknown how an acute exercise bout may modify the circulating expression of hepcidin. Therefore, the current review aims to determine the post-exercise expression of serum hepcidin in response to a single session of exercise. The review was carried out in the Dialnet, Elsevier, Medline, Pubmed, Scielo and SPORTDiscus databases, using hepcidin (and "exercise" or "sport" or "physical activity") as a strategy of search. A total of 19 articles were included in the review after the application of the inclusion/exclusion criteria. This search found that a single session of endurance exercise (intervallic or continuous) at moderate or vigorous intensity (60-90% VO2peak) stimulates an increase in the circulating levels of hepcidin between 0 h and 6 h after the end of the exercise bout, peaking at ~3 h post-exercise. The magnitude of the response of hepcidin to exercise seems to be dependent on the pre-exercise status of iron (ferritin) and inflammation (IL-6). Moreover, oxygen disturbances and the activation of a hypoxia-induced factor during or after exercise may stimulate a reduction of hepcidin expression. Meanwhile, cranberry flavonoids supplementation promotes an anti-oxidant effect that may facilitate the post-exercise expression of hepcidin. Further studies are required to explore the effect of resistance exercise on hepcidin expression.

33 citations


Cites background from "Skeletal muscle IL-15/IL-15Rα and m..."

  • ...IL-15 has been shown to exert pro-inflammatory effects when this cytokine is chronically elevated at baseline [114]; however, in response to a single session of exercise, serum IL-15 is upregulated [115,116], and instead of showing a pro-inflammatory function, this myokine exerts oxidative effects in adipose tissue [117]....

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TL;DR: It is suggested that in older adults with aMCI, not only aerobic but also resistance exercise is effective with regard to increasing neurotrophins, reducing some inflammatory cytokines, and facilitating neurocognitive performance.
Abstract: Background Decreased levels of the neuroprotective growth factors, low-grade inflammation, and reduced neurocognitive functions during aging are associated with neurodegenerative diseases, such as Alzheimer's disease. Physical exercise modifies these disadvantageous phenomena while a sedentary lifestyle promotes them. Purpose The purposes of the present study included investigating whether both aerobic and resistance exercise produce divergent effects on the neuroprotective growth factors, inflammatory cytokines, and neurocognitive performance, and further exploring whether changes in the levels of these molecular biomarkers are associated with alterations in neurocognitive performance. Methods Fifty-five older adults with amnestic MCI (aMCI) were recruited and randomly assigned to an aerobic exercise (AE) group, a resistance exercise (RE) group, or a control group. The assessment included neurocognitive measures [e.g., behavior and event-related potential (ERP)] during a task-switching paradigm, as well as circulating neuroprotective growth factors (e.g., BDNF, IGF-1, VEGF, and FGF-2) and inflammatory cytokine (e.g., TNF-α, IL-1β, IL-6, IL-8, and IL-15) levels at baseline and after either a 16-week aerobic or resistance exercise intervention program or a control period. Results Aerobic and resistance exercise could effectively partially facilitate neurocognitive performance [e.g., accuracy rates (ARs), reaction times during the heterogeneous condition, global switching cost, and ERP P3 amplitude] when the participants performed the task switching paradigm although the ERP P2 components and P3 latency could not be changed. In terms of the circulating molecular biomarkers, the 16-week exercise interventions did not change some parameters (e.g., leptin, VEGF, FGF-2, IL-1β, IL-6, and IL-8). However, the peripheral serum BDNF level was significantly increased, and the levels of insulin, TNF-α, and IL-15 levels were significantly decreased in the AE group, whereas the RE group showed significantly increased IGF-1 levels and decreased IL-15 levels. The relationships between the changes in neurocognitive performance (AR and P3 amplitudes) and the changes in the levels of neurotrophins (BDNF and IGF-1)/inflammatory cytokines (TNF-α) only approached significance. Conclusion These findings suggested that in older adults with aMCI, not only aerobic but also resistance exercise is effective with regard to increasing neurotrophins, reducing some inflammatory cytokines, and facilitating neurocognitive performance. However, the aerobic and resistance exercise modes likely employed divergent molecular mechanisms on neurocognitive facilitation.

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TL;DR: The findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.
Abstract: Chronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration. Cell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration. We identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear. These findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.

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Journal ArticleDOI
TL;DR: The literature is reviewed to propose a model for the regulation of IL-15 by the soluble form ofIL-15Rα, which results in a phenotype similar to that of overexpressing/oversecreting IL- 15 in mice to explain why some findings in the literature seem to be contradictory.
Abstract: Interleukin (IL)-15 is a cytokine with important immunological functions It is highly expressed in skeletal muscle and is believed to be a myokine, a hypothesis supported by the rapid increase in circulating levels of IL-15 in response to exercise Treatment with high doses of IL-15 results in metabolic adaptations such as improved insulin sensitivity and whole-body fatty acid oxidation and protection from high-fat-diet-induced obesity and insulin resistance IL-15 secreted by contracting muscle may therefore act as an endocrine factor to improve adiposity and energy metabolism in different tissues Most studies have used supraphysiological doses of IL-15 that do not represent circulating IL-15 in response to exercise However, evidence shows that IL-15 levels are higher in muscle interstitium and that IL-15 might improve muscle glucose homeostasis and oxidative metabolism in an autocrine/paracrine manner Nevertheless, how IL-15 signals in skeletal muscle to improve muscle energy metabolism is not understood completely, especially because the absence of the α subunit of the IL-15 receptor (IL-15Rα) results in a phenotype similar to that of overexpressing/oversecreting IL-15 in mice In this article, we review the literature to propose a model for the regulation of IL-15 by the soluble form of IL-15Rα to explain why some findings in the literature seem, at first glance, to be contradictory

25 citations


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TL;DR: The results show no overall differences in the myokine response to HIIT or RT, and it is mostly the individual response of each subject rather than general recommendations on type of training session that must be taken into consideration for maximizing cardiometabolic benefits in the context of personalized exercise prescription.
Abstract: Purpose: This study aimed to compare the response to acute exercise of several myokines/hormones involved in metabolic function between two types of training sessions that are growing in popularity for their purported cardiometabolic benefits, high-intensity interval (HIIT) and resistance training (RT). Methods: Seventeen healthy, non-athletic men (23 ± 3 years) participated in this cross-over study. They randomly performed a HIIT [with short (HIIT1) or long (HIIT2) intervals] or a RT session. The concentration of fibroblast-growth factor (FGF) 21, follistatin, ghrelin, interleukin-15, irisin, myostatin, and peptide YY was measured at baseline and 0, 1, 3, 24, 48, and 72 h post-exercise. An individual approach was adopted to determine the rate of responsiveness to each specific cytokine and training mode. Results: A significant condition (session type) by time interaction (p = 0.004) effect was observed for FGF21, with RT eliciting a greater area under the curve (AUC) concentration than HIIT1 (p = 0.02). The AUC for follistatin was significantly greater after HIIT2 compared with RT (p = 0.02). Individual responsiveness to all session types ranged between 19 and 93% depending on the cytokine. However, most subjects (71-100%) responded positively for all cytokines (except for irisin, with only 53% of responders) after 1+ session type. Conclusion: Except for FGF21, our results show no overall differences in the myokine response to HIIT or RT. A considerable individual variability was observed, with some subjects responding to some but not other training session types. Notwithstanding, most responded to at least one training session. Thus, it is mostly the individual response of each subject rather than general recommendations on type of training session (i.e., RT vs. HIIT or HIIT subtypes) that must be taken into consideration for maximizing cardiometabolic benefits in the context of personalized exercise prescription.

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References
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Journal ArticleDOI
13 May 1994-Science
TL;DR: A cytokine was identified that stimulated the proliferation of T lymphocytes, and a complementary DNA clone encoding this new T cell growth factor was isolated, indicating that IL-15 uses components of the IL-2 receptor.
Abstract: A cytokine was identified that stimulated the proliferation of T lymphocytes, and a complementary DNA clone encoding this new T cell growth factor was isolated. The cytokine, designated interleukin-15 (IL-15), is produced by a wide variety of cells and tissues and shares many biological properties with IL-2. Monoclonal antibodies to the beta chain of the IL-2 receptor inhibited the biological activity of IL-15, and IL-15 competed for binding with IL-2, indicating that IL-15 uses components of the IL-2 receptor.

1,403 citations


Journal ArticleDOI
TL;DR: It is concluded that exercise resulted in an increase in muscle net protein balance that persisted for up to 48 h after the exercise bout and was unrelated to the type of muscle contraction performed.
Abstract: Mixed muscle protein fractional synthesis rate (FSR) and fractional breakdown rate (FBR) were examined after an isolated bout of either concentric or eccentric resistance exercise. Subjects were eight untrained volunteers (4 males, 4 females). Mixed muscle protein FSR and FBR were determined using primed constant infusions of [2H5]phenylalanine and 15N-phenylalanine, respectively. Subjects were studied in the fasted state on four occasions: at rest and 3, 24, and 48 h after a resistance exercise bout. Exercise was eight sets of eight concentric or eccentric repetitions at 80% of each subject's concentric 1 repetition maximum. There was no significant difference between contraction types for either FSR, FBR, or net balance (FSR minus FBR). Exercise resulted in significant increases above rest in muscle FSR at all times: 3 h = 112%, 24 h = 65%, 48 h = 34% (P < 0.01). Muscle FBR was also increased by exercise at 3 h (31%; P < 0.05) and 24 h (18%; P < 0.05) postexercise but returned to resting levels by 48 h. Muscle net balance was significantly increased after exercise at all time points [(in %/h) rest = -0.0573 +/- 0.003 (SE), 3 h = -0.0298 +/- 0.003, 24 h = -0.0413 +/- 0.004, and 48 h = -0.0440 +/- 0.005], and was significantly different from zero at all time points (P < 0.05). There was also a significant correlation between FSR and FBR (r = 0.88, P < 0.001). We conclude that exercise resulted in an increase in muscle net protein balance that persisted for up to 48 h after the exercise bout and was unrelated to the type of muscle contraction performed.

1,052 citations


Journal ArticleDOI
TL;DR: Low and intermediate RM training appears to induce similar muscular adaptations, at least after short-term training in previously untrained subjects, and both physical performance and the associated physiological adaptations are linked to the intensity and number of repetitions performed, and thus lend support to the strength–endurance continuum.
Abstract: Thirty-two untrained men [mean (SD) age 22.5 (5.8) years, height 178.3 (7.2) cm, body mass 77.8 (11.9) kg] participated in an 8-week progressive resistance-training program to investigate the "strength–endurance continuum". Subjects were divided into four groups: a low repetition group (Low Rep, n=9) performing 3–5 repetitions maximum (RM) for four sets of each exercise with 3 min rest between sets and exercises, an intermediate repetition group (Int Rep, n=11) performing 9–11 RM for three sets with 2 min rest, a high repetition group (High Rep, n=7) performing 20–28 RM for two sets with 1 min rest, and a non-exercising control group (Con, n=5). Three exercises (leg press, squat, and knee extension) were performed 2 days/week for the first 4 weeks and 3 days/week for the final 4 weeks. Maximal strength [one repetition maximum, 1RM), local muscular endurance (maximal number of repetitions performed with 60% of 1RM), and various cardiorespiratory parameters (e.g., maximum oxygen consumption, pulmonary ventilation, maximal aerobic power, time to exhaustion) were assessed at the beginning and end of the study. In addition, pre- and post-training muscle biopsy samples were analyzed for fiber-type composition, cross-sectional area, myosin heavy chain (MHC) content, and capillarization. Maximal strength improved significantly more for the Low Rep group compared to the other training groups, and the maximal number of repetitions at 60% 1RM improved the most for the High Rep group. In addition, maximal aerobic power and time to exhaustion significantly increased at the end of the study for only the High Rep group. All three major fiber types (types I, IIA, and IIB) hypertrophied for the Low Rep and Int Rep groups, whereas no significant increases were demonstrated for either the High Rep or Con groups. However, the percentage of type IIB fibers decreased, with a concomitant increase in IIAB fibers for all three resistance-trained groups. These fiber-type conversions were supported by a significant decrease in MHCIIb accompanied by a significant increase in MHCIIa. No significant changes in fiber-type composition were found in the control samples. Although all three training regimens resulted in similar fiber-type transformations (IIB to IIA), the low to intermediate repetition resistance-training programs induced a greater hypertrophic effect compared to the high repetition regimen. The High Rep group, however, appeared better adapted for submaximal, prolonged contractions, with significant increases after training in aerobic power and time to exhaustion. Thus, low and intermediate RM training appears to induce similar muscular adaptations, at least after short-term training in previously untrained subjects. Overall, however, these data demonstrate that both physical performance and the associated physiological adaptations are linked to the intensity and number of repetitions performed, and thus lend support to the "strength–endurance continuum".

936 citations


Journal ArticleDOI
Abstract: (1975). Percutaneous Needle Biopsy of Skeletal Muscle in Physiological and Clinical Research. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 35, No. 7, pp. 609-616.

912 citations


Journal ArticleDOI
01 Nov 2002-Immunity
TL;DR: These complexes on activated monocytes present IL-15 in trans to target cells such as CD8 + T cells that express only IL-2/15Rβ and γc upon cell-cell interaction and contribute to the long survival of T cells expressing IL- 15Rα afterIL-15 withdrawal.
Abstract: We report intriguing aspects of the contribution of IL-15Ralpha to IL-15 functions. Consistent with high-affinity interactions between IL-15 and IL-15Ralpha, these two molecules form stable complexes on the cell surface of activated monocytes. The formation of IL-15/IL-15Ralpha complexes on cell surfaces induces a trans-endosomal recycling of IL-15 leading to the persistence of surface-bound IL-15 due to the constant reappearance of IL-15 on plasma membranes. This complex contributes to the long survival of T cells expressing IL-15Ralpha after IL-15 withdrawal. Finally, these complexes on activated monocytes present IL-15 in trans to target cells such as CD8(+) T cells that express only IL-2/15Rbeta and gammac upon cell-cell interaction.

819 citations


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