Interleukin-4 (IL-4) induces down-modulation and shedding of the p55 tumour necrosis factor receptor and inhibits TNF alpha's effect on rheumatoid synovial fibroblasts.
Recombinant human interleukin-4 (rhIL-4) and rhIL-1 alpha each produced a rapid down-modulation of tumour necrosis factor receptor (TNFR) on rheumatoid synovial fibroblasts (RSF) in vitro. This was associated with a staurosporine-resistant increase in p55 soluble TNFR levels, in culture media, suggesting that down-modulation was due to enhanced receptor shedding via a protein kinase C-independent mechanism. Pretreatment with rhIL-4 reduced the subsequent tumour necrosis factor alpha (TNF alpha) stimulation of prostaglandin E (PGE) and matrix metalloproteinase-3 (MMP-3) production by RSF. Thus, the potential anti-synovial monokine properties of rhIL-4 are not confined to inhibiting monokine production but also include the ability to interfere with their action on cells that constitute a substantial proportion of the rheumatoid synovium.
Taylor
D J
DJ
University Department of Medicine, University Hospital of South Manchester, West Didsbury, UK.
D000470:Alkaloids / Q000494:pharmacology; D015703:Antigens, CD; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D015846:Monokines / Q000096:biosynthesis / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000494:pharmacology; D019311:Staurosporine; D013583:Synovial Membrane / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects*
D000470:Alkaloids; D015703:Antigens, CD; D015846:Monokines; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D011493:Protein Kinase C; D019311:Staurosporine