Myocytes respond to both interleukin-4 and interferon-gamma: cytokine responsiveness with the potential to influence the severity and course of experimental myasthenia gravis.
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.
Stegall
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Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7758, USA.
Krolick
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KA
D000818:Animals; D002460:Cell Line; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019409:Interleukin-15; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases