scispace - formally typeset
Search or ask a question
Journal Article•DOI•

Expression of interleukin-15 in human skeletal muscle – effect of exercise and muscle fibre type composition

Anders Rinnov Nielsen, Rémi Mounier, Peter Plomgaard, Ole Hartvig Mortensen, Milena Penkowa1, Tobias Speerschneider2, Henriette Pilegaard2, Bente Klarlund Pedersen •
Panum Institute1, University of Copenhagen2
01 Oct 2007-The Journal of Physiology (J Physiol)-Vol. 584, Iss: 1, pp 305-312
TL;DR: IL‐15 mRNA level is enhanced in skeletal muscles dominated by type 2 fibres and resistance exercise induces increased muscular IL-15 mRNA levels, suggesting that muscle IL‐15 may exist in a translationally inactive pool.
Abstract: The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers (n = 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects (n = 8) not involved in any kind of resistance exercise underwent a heavy resistance exercise protocol that stimulated the vastus lateralis muscle and biopsies were obtained from this muscle pre-exercise as well as 6, 24 and 48 h post-exercise. IL-15 mRNA levels were twofold higher in the triceps (type 2 fibre dominance) compared with the soleus muscle (type 1 fibre dominance), but Western blotting and immunohistochemistry revealed that muscle IL-15 protein content did not differ between triceps brachii, quadriceps and soleus muscles. Following resistance exercise, IL-15 mRNA levels were up-regulated twofold at 24 h of recovery without any changes in muscle IL-15 protein content or plasma IL-15 at any of the investigated time points. In conclusion, IL-15 mRNA level is enhanced in skeletal muscles dominated by type 2 fibres and resistance exercise induces increased muscular IL-15 mRNA levels. IL-15 mRNA levels in skeletal muscle were not paralleled by similar changes in muscular IL-15 protein expression suggesting that muscle IL-15 may exist in a translationally inactive pool.
Citations
More filters
Journal Article•DOI•
Muscle as an endocrine organ: focus on muscle-derived interleukin-6.

[...]

Bente Klarlund Pedersen1, Mark A. Febbraio2•
University of Copenhagen1, Copenhagen University Hospital2
01 Oct 2008-Physiological Reviews
TL;DR: This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.
Abstract: Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "myokines." Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

1,793 citations

Journal Article•
Position statement. Part one: Immune function and exercise.

[...]

Neil P. Walsh, Michael Gleeson1, Roy J. Shephard2, Jeffrey A. Woods, Nicolette C. Bishop1, Monika Fleshner3, Charlotte J. Green4, Bente Klarlund Pedersen4, Laurie Hoffman-Goetz5, Connie J. Rogers6, Hinnak Northoff7, Asghar Abbasi7, Perikles Simon8 •
Loughborough University1, University of Toronto2, University of Colorado Boulder3, University of Copenhagen4, University of Waterloo5, Pennsylvania State University6, University of Tübingen7, University of Mainz8
01 Jan 2011-Exercise Immunology Review
TL;DR: The epidemiological distinction between the generic term "physical activity" and the specific category of "exercise", which implies activity for a specific purpose such as improvement of physical condition or competition is recognised.
Abstract: An ever-growing volume of peer-reviewed publications speaks to the recent and rapid growth in both scope and understanding of exercise immunology. Indeed, more than 95% of all peer-reviewed publications in exercise immunology (currently >2, 200 publications using search terms "exercise" and "immune") have been published since the formation of the International Society of Exercise and Immunology (ISEI) in 1989 (ISI Web of Knowledge). We recognise the epidemiological distinction between the generic term "physical activity" and the specific category of "exercise", which implies activity for a specific purpose such as improvement of physical condition or competition. Extreme physical activity of any type may have implications for the immune system. However, because of its emotive component, exercise is likely to have a larger effect, and to date the great majority of our knowledge on this subject comes from exercise studies.

1,260 citations

Cites background from "Expression of interleukin-15 in hum..."

  • ...IL-15 mRNA levels are upregulated in human skeletal muscle following a bout of strength training (190), suggesting that regular training may lead to IL-15 accumulation within muscle....

    [...]

Journal Article•DOI•
Molecular inflammation: underpinnings of aging and age-related diseases.

[...]

Hae Young Chung1, Matteo Cesari2, Stephen D. Anton2, Emanuele Marzetti2, Silvia Giovannini2, Arnold Y. Seo2, Christy S. Carter2, Byung Pal Yu3, Christiaan Leeuwenburgh2 •
Pusan National University1, University of Florida2, University of Texas Health Science Center at San Antonio3
01 Jan 2009-Ageing Research Reviews
TL;DR: The purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging to provide insights into potential interventions that may affect the aging process and reduce age- related diseases, thereby promoting healthy longevity.

1,029 citations

Cites background from "Expression of interleukin-15 in hum..."

  • ...N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript IL-10 has been shown to inhibit the synthesis of several pro-inflammatory cytokines, including TNF-α and IL-1β (Nielsen et al., 2007)....

    [...]

  • ...IL-10 has been shown to inhibit the synthesis of several pro-inflammatory cytokines, including TNF-α and IL-1β (Nielsen et al., 2007)....

    [...]

Journal Article•DOI•
Exercise is the Real Polypill

[...]

Carmen Fiuza-Luces1, Nuria Garatachea2, Nathan A. Berger3, Alejandro Lucia1•
European University of Madrid1, University of Zaragoza2, Case Western Reserve University3
01 Sep 2013-Physiology
TL;DR: In this article, a review summarizes the current body of knowledge on the main biological mediators (ingredients) of the preventive/therapeutic effects of regular exercise, and summarizes their roles.
Abstract: This review summarizes the current body of knowledge on the main biological mediators (ingredients) of the preventive/therapeutic effects of regular exercise.

574 citations

Cites background from "Expression of interleukin-15 in hum..."

  • ...Another prototype of contraction-induced myokine is IL-15, with resistance exercise stimulating its secretion (338, 402)....

    [...]

  • ...In addition to its local anabolic/anti-catabolic effects (59, 60, 135, 338, 390, 391), IL-15 plays an anti-obesogenic effect (337, 388), mainly by inhibiting lipid deposition (8 –10, 24, 59, 136, 389)....

    [...]

Journal Article•DOI•
Muscles and their myokines

[...]

Bente Klarlund Pedersen
15 Jan 2011-The Journal of Experimental Biology
TL;DR: The discovery that contracting skeletal muscle secretes proteins sets a novel paradigm: skeletal muscle is an endocrine organ producing and releasing myokines, which work in a hormone-like fashion, exerting specific endocrine effects on other organs.
Abstract: In the past, the role of physical activity as a life-style modulating factor has been considered as that of a tool to balance energy intake. Although it is important to avoid obesity, physical inactivity should be discussed in a much broader context. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular diseases, cancer, dementia and even depression. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an 'exercise factor', which could be released from skeletal muscle during contraction and mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We have suggested that cytokines or other peptides that are produced, expressed and released by muscle fibres and exert autocrine, paracrine or endocrine effects should be classified as 'myokines'. Given that skeletal muscle is the largest organ in the human body, our discovery that contracting skeletal muscle secretes proteins sets a novel paradigm: skeletal muscle is an endocrine organ producing and releasing myokines, which work in a hormone-like fashion, exerting specific endocrine effects on other organs. Other myokines work via paracrine mechanisms, exerting local effects on signalling pathways involved in muscle metabolism. It has been suggested that myokines may contribute to exercise-induced protection against several chronic diseases.

562 citations

Cites background from "Expression of interleukin-15 in hum..."

  • ...Recently, we demonstrated that IL-15 mRNA levels were upregulated in human skeletal muscle following a bout of strength training (Nielsen et al., 2007), suggesting that IL-15 may accumulate within the muscle as a consequence of regular training....

    [...]

References
More filters
Journal Article•DOI•
Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor

[...]

Kenneth H. Grabstein, June R. Eisenman, Kurt D. Shanebeck, Charles Rauch, Subhashini Srinivasan, Victor Fung, Courtney Beers, Jane S. Richardson, Michael A. Schoenborn, Minoo Ahdieh, Lisabeth Johnson, Mark R. Alderson, James D. Watson, Dirk M. Anderson, Judith G. Giri 
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.

1,441 citations

"Expression of interleukin-15 in hum..." refers background in this paper

  • ...Email: bkp@rh.dk The cytokine interleukin-15 (IL-15) is a recently discovered growth factor, which is expressed in skeletal muscle (Grabstein et al. 1994) and has been suggested to play a role in muscle–adipose tissue interaction (Argiles et al. 2005)....

    [...]

  • ...The cytokine interleukin-15 (IL-15) is a recently discovered growth factor, which is expressed in skeletal muscle (Grabstein et al. 1994) and has been suggested to play a role in muscle–adipose tissue interaction (Argiles et al....

    [...]

  • ...The IL-15 mRNA was shown by Grabstein et al. (1994) to be expressed in human muscle....

    [...]

  • ...The expression of IL-15 mRNA has been found in many distinct tissues (Grabstein et al. 1994; Giri et al. 1995)....

    [...]

Journal Article•DOI•
Percutaneous Needle Biopsy of Skeletal Muscle in Physiological and Clinical Research

[...]

Jonas Bergström
01 Nov 1975-Scandinavian Journal of Clinical & Laboratory Investigation
TL;DR: In this article, a percutaneous needle biopsy of skeletal muscle in Physiological and Clinical Research is described, and the authors present a detailed discussion of the procedure and the results.
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.

944 citations

Journal Article•DOI•
Muscle-derived interleukin-6: mechanisms for activation and possible biological roles

[...]

Mark A. Febbraio1, Bente Klarlund Pedersen1•
University of Copenhagen1
01 Sep 2002-The FASEB Journal
TL;DR: It appears that intramuscular IL‐6 is stimulated by complex signaling cascades initiated by both calcium (Ca2+) ‐dependent and ‐independent stimuli, and it also seems likely that skeletal muscle produces IL‐ 6 to aid in maintaining metabolic homeostasis during periods of altered metabolic demand such as muscular exercise or insulin stimulation.
Abstract: It has recently been demonstrated that the marked increase in the systemic concentration of cytokine interleukin-6 (IL-6) seen with exercise originates from the contracting limb and that skeletal muscle cells per se are the likely source of the production. This review summarizes the possible mechanisms for activation and biological consequences of muscle-derived IL-6. It appears that intramuscular IL-6 is stimulated by complex signaling cascades initiated by both calcium (Ca2+) -dependent and -independent stimuli. It also seems likely that skeletal muscle produces IL-6 to aid in maintaining metabolic homeostasis during periods of altered metabolic demand such as muscular exercise or insulin stimulation. It may do so via local and/or systemic effects. This review also explores the efficacy that IL-6 may be used as a therapeutic drug in treating metabolic disorders such as obesity, type 2 diabetes, and atherosclerosis.—Febbraio, M. A., Pedersen, B. K. Muscle-derived interleukin 6: mechanisms for activation ...

868 citations

"Expression of interleukin-15 in hum..." refers background in this paper

  • ...Among these cytokines, solid evidence exists that IL-6 (Pedersen et al. 2003a,b; Febbraio & Pedersen, 2002, 2005) and IL-8 (Nieman et al. 2003; Chan et al. 2004; Akerstrom et al. 2005) are regulated by muscle contractions – both at the mRNA and the protein level....

    [...]

Journal Article•DOI•
Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor.

[...]

J. G. Giri, S Kumaki, M Ahdieh, D. J. Friend, A. Loomis, K. Shanebeck, R. DuBose, David Cosman, L S Park, Dirk M. Anderson 
01 Aug 1995-The EMBO Journal
TL;DR: The characterization and molecular cloning of a distinct murine IL‐15R alpha chain is reported, which displays an affinity of binding forIL‐15 equivalent to that of the heterotrimericIL‐2R for IL‐2.
Abstract: Interleukin-15 (IL-15) is a novel cytokine of the four-helix bundle family which shares many biological activities with IL-2, probably due to its interaction with the IL-2 receptor beta and gamma (IL-2R beta and gamma c) chains. We report here the characterization and molecular cloning of a distinct murine IL-15R alpha chain. IL-15R alpha alone displays an affinity of binding for IL-15 equivalent to that of the heterotrimeric IL-2R for IL-2. A biologically functional heteromeric IL-15 receptor complex capable of mediating IL-15 responses was generated through reconstruction experiments in a murine myeloid cell line. IL-15R alpha is structurally similar to IL-2R alpha; together they define a new cytokine receptor family. The distribution of IL-15 and IL-15R alpha mRNA suggests that IL-15 may have biological activities distinct from IL-2.

616 citations

"Expression of interleukin-15 in hum..." refers background in this paper

  • ...The expression of IL-15 mRNA has been found in many distinct tissues (Grabstein et al. 1994; Giri et al. 1995)....

    [...]

Journal Article•DOI•
Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise

[...]

Henriette Pilegaard1, Henriette Pilegaard2, G. A. Ordway3, Bengt Saltin2, P. Darrell Neufer1 •
Yale University1, University of Copenhagen2, University of Texas Southwestern Medical Center3
01 Oct 2000-American Journal of Physiology-endocrinology and Metabolism
TL;DR: It is demonstrated that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle, and the findings suggest that the cumulative effects of transient rises in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.
Abstract: Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise tr...

567 citations

"Expression of interleukin-15 in hum..." refers methods in this paper

  • ...…μg total RNA was reverse transcribed either in a total volume of 100 μl using Taqman Reverse Transcription Kit (Applied Biosystems, NJ, USA) and random hexamers as primers or using the Superscript II RNase H− system (Invitrogen, CA, USA) and oligo dT as previously described (Pilegaard et al. 2000)....

    [...]

  • ...The RNA concentration was determined spectrophotometrically and 2 μg total RNA was reverse transcribed either in a total volume of 100 μl using Taqman Reverse Transcription Kit (Applied Biosystems, NJ, USA) and random hexamers as primers or using the Superscript II RNase H− system (Invitrogen, CA, USA) and oligo dT as previously described (Pilegaard et al. 2000)....

    [...]

  • ...…total RNA was extracted from ∼50 mg muscle tissue using TRIzol Reagent (Invitrogen, Carlsbad, USA) following the manufacture’s instruction or from ∼25 mg of muscle tissue by a modified guanidinium thiocyanate (GT)–phenol–chloroform extraction method as previously described (Pilegaard et al. 2000)....

    [...]

  • ...In both studies, total RNA was extracted from ∼50 mg muscle tissue using TRIzol Reagent (Invitrogen, Carlsbad, USA) following the manufacture’s instruction or from ∼25 mg of muscle tissue by a modified guanidinium thiocyanate (GT)–phenol–chloroform extraction method as previously described (Pilegaard et al. 2000)....

    [...]

Related Papers (5)
Muscle as an endocrine organ: focus on muscle-derived interleukin-6.

[...]

01 Oct 2008-Physiological Reviews
Bente Klarlund Pedersen, Mark A. Febbraio
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis

[...]

26 Jan 2012-Nature
Pontus Boström, Jun Wu, Mark P. Jedrychowski, Anisha Korde, Li Ye, James C. Lo, Kyle A. Rasbach, Elisabeth A. Boström, Jang Hyun Choi, Jonathan Z. Long, Shingo Kajimura, Maria Cristina Zingaretti, Birgitte F. Vind, Hua Tu, Saverio Cinti, Kurt Højlund, Steven P. Gygi, Bruce M. Spiegelman 
Role of myokines in exercise and metabolism.

[...]

01 Sep 2007-Journal of Applied Physiology
Bente Klarlund Pedersen, Thorbjorn Akerstrom, Anders Rinnov Nielsen, Christian P. Fischer 
Production of interleukin‐6 in contracting human skeletal muscles can account for the exercise‐induced increase in plasma interleukin‐6

[...]

01 Nov 2000-The Journal of Physiology
Adam Steensberg, Gerrit van Hall, Takuya Osada, Massimo Sacchetti, Bengt Saltin, Bente Klarlund Pedersen 
Muscles, exercise and obesity: skeletal muscle as a secretory organ

[...]

03 Apr 2012-Nature Reviews Endocrinology
Bente Klarlund Pedersen, Mark A. Febbraio