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Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha.
J Immunol. 1991 May 15; 146(10):3365-71.JI

Abstract

Granulocyte-macrophage CSF (GM-CSF) is a potent stimulator of macrophages and neutrophils and is produced by rheumatoid arthritis (RA) synovium. We now report studies that identify some of the synovial cells and cytokines responsible for local GM-CSF production and gene expression in RA. GM-CSF was assayed by ELISA in supernatants from cultured RA fibroblast-like synoviocytes stimulated with various cytokines (IL-1 beta, TNF-alpha, macrophage-CSF, IFN-gamma, IL-6, and TGF-beta). Immunoreactive GM-CSF was detected in IL-1 beta and TNF-alpha-stimulated cultures, but not in cells cultured in medium or stimulated with any of the other cytokines. IL-1 and TNF-alpha had a synergistic effect on GM-CSF production. GM-CSF gene expression by fibroblast-like synoviocytes was analyzed by ribonuclease protection assay, Northern blot analysis, and in situ hybridization. Both IL-1 beta and TNF-alpha induced GM-CSF mRNA accumulation, with a maximum effect after 4 h of stimulation. We then studied GM-CSF production by macrophage-like synoviocytes (MLS) isolated from fresh synovial specimens by flow microfluorimetry. Fresh MLS spontaneously secreted the cytokine and exogenous IL-1 beta or TNF-alpha had no effect. After 1 wk in culture, additional stimulation with IL-1 beta or TNF-alpha was required for GM-CSF production. Finally, in situ hybridization performed on freshly isolated subpopulations of synovial cells, identified GM-CSF RNA transcripts in MLS.

Authors+Show Affiliations

Division of Rheumatology, University of California, San Diego 92103.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2026869

Citation

Alvaro-Gracia, J M., et al. "Cytokines in Chronic Inflammatory Arthritis. VI. Analysis of the Synovial Cells Involved in Granulocyte-macrophage Colony-stimulating Factor Production and Gene Expression in Rheumatoid Arthritis and Its Regulation By IL-1 and Tumor Necrosis Factor-alpha." Journal of Immunology (Baltimore, Md. : 1950), vol. 146, no. 10, 1991, pp. 3365-71.
Alvaro-Gracia JM, Zvaifler NJ, Brown CB, et al. Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha. J Immunol. 1991;146(10):3365-71.
Alvaro-Gracia, J. M., Zvaifler, N. J., Brown, C. B., Kaushansky, K., & Firestein, G. S. (1991). Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha. Journal of Immunology (Baltimore, Md. : 1950), 146(10), 3365-71.
Alvaro-Gracia JM, et al. Cytokines in Chronic Inflammatory Arthritis. VI. Analysis of the Synovial Cells Involved in Granulocyte-macrophage Colony-stimulating Factor Production and Gene Expression in Rheumatoid Arthritis and Its Regulation By IL-1 and Tumor Necrosis Factor-alpha. J Immunol. 1991 May 15;146(10):3365-71. PubMed PMID: 2026869.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha. AU - Alvaro-Gracia,J M, AU - Zvaifler,N J, AU - Brown,C B, AU - Kaushansky,K, AU - Firestein,G S, PY - 1991/5/15/pubmed PY - 1991/5/15/medline PY - 1991/5/15/entrez SP - 3365 EP - 71 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 146 IS - 10 N2 - Granulocyte-macrophage CSF (GM-CSF) is a potent stimulator of macrophages and neutrophils and is produced by rheumatoid arthritis (RA) synovium. We now report studies that identify some of the synovial cells and cytokines responsible for local GM-CSF production and gene expression in RA. GM-CSF was assayed by ELISA in supernatants from cultured RA fibroblast-like synoviocytes stimulated with various cytokines (IL-1 beta, TNF-alpha, macrophage-CSF, IFN-gamma, IL-6, and TGF-beta). Immunoreactive GM-CSF was detected in IL-1 beta and TNF-alpha-stimulated cultures, but not in cells cultured in medium or stimulated with any of the other cytokines. IL-1 and TNF-alpha had a synergistic effect on GM-CSF production. GM-CSF gene expression by fibroblast-like synoviocytes was analyzed by ribonuclease protection assay, Northern blot analysis, and in situ hybridization. Both IL-1 beta and TNF-alpha induced GM-CSF mRNA accumulation, with a maximum effect after 4 h of stimulation. We then studied GM-CSF production by macrophage-like synoviocytes (MLS) isolated from fresh synovial specimens by flow microfluorimetry. Fresh MLS spontaneously secreted the cytokine and exogenous IL-1 beta or TNF-alpha had no effect. After 1 wk in culture, additional stimulation with IL-1 beta or TNF-alpha was required for GM-CSF production. Finally, in situ hybridization performed on freshly isolated subpopulations of synovial cells, identified GM-CSF RNA transcripts in MLS. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/2026869/Cytokines_in_chronic_inflammatory_arthritis__VI__Analysis_of_the_synovial_cells_involved_in_granulocyte_macrophage_colony_stimulating_factor_production_and_gene_expression_in_rheumatoid_arthritis_and_its_regulation_by_IL_1_and_tumor_necrosis_factor_alpha_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=2026869 DB - PRIME DP - Unbound Medicine ER -