title: Contribution of tumour necrosis factor alpha and interleukin (IL) 1beta to IL6 production, NF-kappaB nuclear translocation, and class I MHC expression in muscle cells: in vitro regulation with specific cytokine inhibitors.
abstract: OBJECTIVE
  To evaluate the effect of tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, and their respective inhibitors the p75 TNFalpha soluble receptor (sTNFR) and the type II sIL1betaR (sIL1RII) on whole muscle and isolated myoblast activation.
  
  
  METHODS
  Normal muscle samples were stimulated for 7 days with TNFalpha alone or in combination with IL1beta, and myoblasts from these samples for 48 hours. IL6 production was measured by ELISA. Nuclear translocation of NF-kappaB was analysed by immunofluorescent staining and class I MHC expression by FACS.
  
  
  RESULTS
  TNFalpha and IL1beta induced IL6 production by normal muscle samples and myoblasts, the action of TNFalpha being more potent on muscle samples. Their soluble receptors (1 microg/ml) decreased this production. Suboptimal concentrations of TNFalpha and IL1beta induced NF-kappaB translocation. sTNFR markedly down regulated TNFalpha-induced translocation while sIL1RII was less potent on IL1beta-induced activation. NF-kappaB translocation induced by the combination of optimal concentrations of TNFalpha and IL1beta was completely inhibited by their soluble receptors. TNFalpha and to a lesser extent IL1beta induced class I MHC expression by myoblasts and this effect was completely inhibited by their respective soluble receptors.
  
  
  CONCLUSIONS
  These results suggest that TNFalpha and IL1beta should be targeted for myositis treatment.
authors.affiliation: Departments of Immunology and Rheumatology and INSERM Unit 403, Hôpital E, Herriot, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Chevrel
authors.forename: C
authors.initials: C
authors.lastname: Granet
authors.forename: P
authors.initials: P
authors.lastname: Miossec
mesh_terms: D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D000068800:Etanercept; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014178:Translocation, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
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