Myocytes respond to both interleukin-4 and interferon-gamma: cytokine responsiveness with the potential to influence the severity and course of experimental myasthenia gravis

Clin Immunol. 2000 Feb;94(2):133-9. doi: 10.1006/clim.1999.4822.

Abstract

Messenger RNA that encodes for interleukin-15 (IL-15) has been reported to be constitutively expressed in skeletal muscle, although the protein product is not generally observed. Furthermore, interferon-gamma (IFN-gamma) has been reported to exacerbate symptoms of experimental myasthenia gravis (EAMG). Therefore, since IL-15 is an activator of IFN-gamma-producing cells, the hypothesis that drove the study reported below proposes that muscle is not a passive participant in the development of disease symptoms in EAMG and, in fact, plays a very important active role by producing immunomodulating factors that can influence the eventual immunopathological impact of the immune system on muscle. Tests of this hypothesis, made using a monoclonal skeletal myocyte line from the Lewis rat, have indicated that myocytes produce IL-15 protein following exposure to interleukin-4 (IL-4), an interesting paradox in light of the usual anti-inflammatory role played by IL-4. Furthermore, the level of IL-15 also can be regulated by IFN-gamma itself. Although yet to be confirmed in vivo, IFN-gamma has been shown to be capable of activating cultured myocytes in a variety of ways that could influence the ongoing autoimmune response associated with EAMG.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Immunohistochemistry
  • Interferon-gamma / pharmacology*
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism
  • Interleukin-4 / pharmacology*
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / immunology*
  • Myasthenia Gravis, Autoimmune, Experimental / immunology*
  • Myasthenia Gravis, Autoimmune, Experimental / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Interleukin-15
  • RNA, Messenger
  • Interleukin-4
  • Interferon-gamma
  • Glyceraldehyde-3-Phosphate Dehydrogenases