Article Text
Abstract
Objective: To evaluate the effect of tumour necrosis factor α (TNFα), interleukin (IL) 1β, and their respective inhibitors the p75 TNFα soluble receptor (sTNFR) and the type II sIL1βR (sIL1RII) on whole muscle and isolated myoblast activation.
Methods: Normal muscle samples were stimulated for 7 days with TNFα alone or in combination with IL1β, and myoblasts from these samples for 48 hours. IL6 production was measured by ELISA. Nuclear translocation of NF-κB was analysed by immunofluorescent staining and class I MHC expression by FACS.
Results: TNFα and IL1β induced IL6 production by normal muscle samples and myoblasts, the action of TNFα being more potent on muscle samples. Their soluble receptors (1 μg/ml) decreased this production. Suboptimal concentrations of TNFα and IL1β induced NF-κB translocation. sTNFR markedly down regulated TNFα-induced translocation while sIL1RII was less potent on IL1β-induced activation. NF-κB translocation induced by the combination of optimal concentrations of TNFα and IL1β was completely inhibited by their soluble receptors. TNFα and to a lesser extent IL1β induced class I MHC expression by myoblasts and this effect was completely inhibited by their respective soluble receptors.
Conclusion: These results suggest that TNFα and IL1β should be targeted for myositis treatment.
- DMEM, Dulbecco’s modified Eagle’s medium
- ELISA, enzyme linked immunosorbent assay
- FACS, fluorescence activated cell sorter
- FCS, fetal calf serum
- FITC, fluorescein isothiocyanate
- IL1β, interleukin 1β
- IIM, idiopathic inflammatory myopathies
- MHC, major histocompatibility complex
- NF-κB, nuclear factor κB
- PBS, phosphate buffered saline
- RA, rheumatoid arthritis
- sR, soluble receptor(s)
- TNFα, tumour necrosis factor α
- interleukin 1
- myoblasts
- myositis
- soluble receptors
- tumour necrosis factor α
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- DMEM, Dulbecco’s modified Eagle’s medium
- ELISA, enzyme linked immunosorbent assay
- FACS, fluorescence activated cell sorter
- FCS, fetal calf serum
- FITC, fluorescein isothiocyanate
- IL1β, interleukin 1β
- IIM, idiopathic inflammatory myopathies
- MHC, major histocompatibility complex
- NF-κB, nuclear factor κB
- PBS, phosphate buffered saline
- RA, rheumatoid arthritis
- sR, soluble receptor(s)
- TNFα, tumour necrosis factor α
Footnotes
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Published Online First 24 February 2005