PMID- 2510238 OWN - NLM STAT- MEDLINE DCOM- 19891215 LR - 20191022 IS - 0172-8172 (Print) IS - 0172-8172 (Linking) VI - 9 IP - 2 DP - 1989 TI - Comparative and combined effects of transforming growth factors alpha and beta, interleukin-1 and interferon-gamma on rheumatoid synovial cell proliferation, glycolysis and prostaglandin E production. PG - 65-70 AB - Enhanced cell proliferation, glycolysis and prostaglandin E production are all characteristic features of rheumatoid synovial tissue. The interrelationships of these three cellular parameters have been examined using rheumatoid synovial fibroblasts and their responses to specific cytokines in vitro. Transforming growth factor alpha (TGF alpha) caused a more than threefold increase in synovial cell proliferation whilst transforming growth factor beta (TGF beta), interleukin-1 alpha (IL-1 alpha) and interferon-gamma (IFN-gamma) produced only marginal changes. The combined addition of IL-1 alpha with TGF beta resulted in an enhanced proliferative response comparable with that produced by TGF alpha. Glycolysis, estimated by glucose utilisation and measurements of the glycolytic regulatory metabolite fructose 2,6-bisphosphate was significantly stimulated by TGF beta, IL-1 alpha and IFN-gamma, but less so by TGF alpha. Prostaglandin E production was significantly increased by IL-1 alpha to an extent much greater than that produced by TGF alpha or TGF beta, although the combined addition of IL-1 alpha with either TGF alpha or beta resulted in a synergistic increase in PGE production, a response partly diminished by the addition of IFN-gamma. These findings suggest that the extent to which a cytokine stimulates glycolysis is not consistently related to its mitogenicity, and that cytokine combinations which stimulate high levels of PGE production (a growth inhibitor) will not necessarily be associated with a reduced rate of cellular proliferation in cultured, adherent, rheumatoid synovial fibroblasts. FAU - Taylor, D J AU - Taylor DJ AD - University Department of Medicine, University Hospital of South Manchester, West Didsbury, UK. FAU - Feldmann, M AU - Feldmann M FAU - Evanson, J M AU - Evanson JM FAU - Woolley, D E AU - Woolley DE LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Rheumatol Int JT - Rheumatology international JID - 8206885 RN - 0 (Biological Factors) RN - 0 (Cytokines) RN - 0 (Interleukin-1) RN - 0 (Prostaglandins E) RN - 76057-06-2 (Transforming Growth Factors) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Biological Factors/*pharmacology MH - Cell Division/drug effects MH - Cytokines MH - Glycolysis/drug effects MH - Humans MH - In Vitro Techniques MH - Interferon-gamma/pharmacology MH - Interleukin-1/pharmacology MH - Prostaglandins E/biosynthesis MH - Rheumatic Diseases/metabolism/*pathology MH - Synovial Membrane/*drug effects/metabolism/pathology MH - Transforming Growth Factors/pharmacology EDAT- 1989/01/01 00:00 MHDA- 1989/01/01 00:01 CRDT- 1989/01/01 00:00 PHST- 1989/01/01 00:00 [pubmed] PHST- 1989/01/01 00:01 [medline] PHST- 1989/01/01 00:00 [entrez] AID - 10.1007/BF00270247 [doi] PST - ppublish SO - Rheumatol Int. 1989;9(2):65-70. doi: 10.1007/BF00270247.