Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Role of IL-15 in Sepsis-Induced Skeletal Muscle Atrophy and Proteolysis

  • Kim, Ho Cheol (Department of Internal Medicine, Institute of Health Science, Gyeongsang National University School of Medicine) ;
  • Cho, Hee-Young (Gyeongsang National University Hospital, Biomedical Research Institute) ;
  • Hah, Young-Sool (Gyeongsang National University Hospital, Biomedical Research Institute)
  • Received : 2012.09.07
  • Accepted : 2012.12.10
  • Published : 2012.12.30
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Abstract

Background: Muscle wasting in sepsis is associated with increased proteolysis. Interleukin-15 (IL-15) has been characterized as an anabolic factor for skeletal muscles. Our study aims to investigate the role of IL-15 in sepsis-induced muscle atrophy and proteolysis. Methods: Mice were rendered septic either by cecal ligation and puncture or by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg i.p.). Expression of IL-15 mRNA and protein was determined by reverse transcriptase polymerase chain reaction and Western blot analysis in the control and septic limb muscles. C2C12 skeletal muscle cells were stimulated in vitro with either LPS or dexamethasone in the presence and absence of IL-15 and sampled at different time intervals (24, 48, or 72 hours). IL-15 ($10{\mu}g/kg$) was intraperitoneally administered 6 hours before sepsis induction and limb muscles were sampled after 24 hours of sepsis. Cathepsin L activity was determined to measure muscle proteolysis. Atrogin-1 and muscle-specific ring finger protein 1 (MuRF1) expressions in limb muscle protein lysates was analyzed. Results: IL-15 mRNA expression was significantly lower in the limb muscles of septic mice compared to that of controls. Cathepsin L activity in C2C12 cells was significantly lower in presence of IL-15, when compared to that observed with individual treatments of LPS or dexamethasone or tumor necrosis factor ${\alpha}$. Further, the limb muscles of mice pre-treated with IL-15 prior to sepsis induction showed a lower expression of atrogin-1 and MuRF1 than those not pre-treated. Conclusion: IL-15 may play a role in protection against sepsis-induced muscle wasting; thereby, serving as a potential therapeutic target for sepsis-induced skeletal muscle wasting and proteolysis.

Keywords

References

  1. Hasselgren PO, Menconi MJ, Fareed MU, Yang H, Wei W, Evenson A. Novel aspects on the regulation of muscle wasting in sepsis. Int J Biochem Cell Biol 2005; 37:2156-68.
  2. Lee GD, Kim HC. Mechanisms of muscle wasting in patients with sepsis. Korean J Crit Care Med 2010;25:9-15.
  3. Lever A, Mackenzie I. Sepsis: definition, epidemiology, and diagnosis. BMJ 2007;335:879-83.
  4. Voisin L, Breuille D, Combaret L, Pouyet C, Taillandier D, Aurousseau E, et al. Muscle wasting in a rat model of long-lasting sepsis results from the activation of lysosomal, Ca2+-activated, and ubiquitin-proteasome proteolytic pathways. J Clin Invest 1996;97:1610-7.
  5. Ulloa L, Tracey KJ. The "cytokine profile": a code for sepsis. Trends Mol Med 2005;11:56-63.
  6. Pajak B, Orzechowska S, Pijet B, Pijet M, Pogorzelska A, Gajkowska B, et al. Crossroads of cytokine signaling: the chase to stop muscle cachexia. J Physiol Pharmacol 2008;59 Suppl 9:251-64.
  7. Li YP, Schwartz RJ, Waddell ID, Holloway BR, Reid MB. Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor necrosis factor alpha. FASEB J 1998;12:871-80.
  8. Di Sabatino A, Calarota SA, Vidali F, Macdonald TT, Corazza GR. Role of IL-15 in immune-mediated and infectious diseases. Cytokine Growth Factor Rev 2011;22:19-33.
  9. Furmanczyk PS, Quinn LS. Interleukin-15 increases myosin accretion in human skeletal myogenic cultures. Cell Biol Int 2003;27:845-51.
  10. Quinn LS, Haugk KL, Grabstein KH. Interleukin-15: a novel anabolic cytokine for skeletal muscle. Endocrinology 1995;136:3669-72.
  11. Quinn LS, Haugk KL, Damon SE. Interleukin-15 stimulates C2 skeletal myoblast differentiation. Biochem Biophys Res Commun 1997;239:6-10.
  12. Maier S, Traeger T, Entleutner M, Westerholt A, Kleist B, Hüser N, et al. Cecal ligation and puncture versus colon ascendens stent peritonitis: two distinct animal models for polymicrobial sepsis. Shock 2004;21:505-11.
  13. Attaix D, Ventadour S, Codran A, Bechet D, Taillandier D, Combaret L. The ubiquitin-proteasome system and skeletal muscle wasting. Essays Biochem 2005;41:173-86.
  14. Carbo N, Lopez-Soriano J, Costelli P, Busquets S, Alvarez B, Baccino FM, et al. Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats. Br J Cancer 2000;83:526-31.
  15. Nielsen AR, Mounier R, Plomgaard P, Mortensen OH, Penkowa M, Speerschneider T, et al. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition. J Physiol 2007; 584(Pt 1):305-12.
  16. Minnaard R, Drost MR, Wagenmakers AJ, van Kranenburg GP, Kuipers H, Hesselink MK. Skeletal muscle wasting and contractile performance in septic rats. Muscle Nerve 2005;31:339-48.
  17. Smith IJ, Lecker SH, Hasselgren PO. Calpain activity and muscle wasting in sepsis. Am J Physiol Endocrinol Metab 2008;295:E762-71.
  18. Figueras M, Busquets S, Carbo N, Barreiro E, Almendro V, Argiles JM, et al. Interleukin-15 is able to suppress the increased DNA fragmentation associated with muscle wasting in tumour-bearing rats. FEBS Lett 2004; 569:201-6.
  19. Harcourt LJ, Holmes AG, Gregorevic P, Schertzer JD, Stupka N, Plant DR, et al. Interleukin-15 administration improves diaphragm muscle pathology and function in dystrophic mdx mice. Am J Pathol 2005;166:1131-41.

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