Involvement of interleukin-6 in activation of lysosomal cathepsin and atrophy of muscle fibers induced by intramuscular injection of turpentine oil in mice.
Serum IL-6 level increased after the injection of turpentine oil into the right gastrocnemius muscle in mice. The mRNA level of IL-6 was highest in the injected muscle at 12 h after injection, but was not identified in the opposite muscle. The activities of cathepsins B and B+L started to elevate after 12 h in the injected muscle and markedly increased after day 3. Likewise, the mRNA levels of cathepsins B and L markedly increased from day 1 to day 5 in the injected muscle. However, a very mild increase was also observed in the opposite muscle. Immunohistochemical staining of cathepsins B and L exhibited positive reactions as fine granules in myofibers at 12 h and strong positive reactions in the infiltrating macrophages at 3 days. Atrophy of myofibers type 1 and 2 was evident in a time-dependent manner in the injected muscle. Treatment with rat anti-mouse IL-6 receptor monoclonal antibody inhibited the increase in cathepsin activities in the injected muscle. We conclude that IL-6 produced in the inflamed muscle is involved in the process of muscle degeneration, especially through the activation of lysosomal cathepsins.
Tsujinaka
T
T
Department of Surgery II, Osaka University Medical School, Suita.
Kishibuchi
M
M
Yano
M
M
Morimoto
T
T
Ebisui
C
C
Fujita
J
J
Ogawa
A
A
Shiozaki
H
H
Kominami
E
E
Monden
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015152:Blotting, Northern; D002401:Cathepsin B / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D015850:Interleukin-6 / Q000097:blood* / Q000502:physiology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000187:drug effects / Q000276:immunology; D014425:Turpentine / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat; D014425:Turpentine