Recombinant human tumor necrosis factors α and β stimulate fibroblasts to produce hemopoietic growth factors in vitro

J. R. Zucali, H. E. Broxmeyer, M. A. Gross, C. A. Dinarello

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

The influences of TNFα and TNFβ were evaluated for their stimulatory and inhibitory effects on in vitro colony formation by human bone marrow granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. Both TNFα and TNFβ induced fibroblasts to produce stimulators of CFU-GM, BFU-E, and CFU-GEMM in a dose-dependent fashion. Similar results were seen when equivalent concentrations of TNFα and TNFβ were used. Prior incubation of the TNFα and TNFβ with their respective antibodies inactivated the ability of the TNF preparations to induce the release of granulocyte-macrophage, erythyroid, and multipotential colony-stimulating activity from fibroblasts. In addition, incubation of the TNF-induced fibroblast supernatant with antibody before colony assay resulted in enhanced colony formation, suggesting that the TNF carried over into the colony assay suppressed colony formation. Additional proof of this suppression by TNF was evident when TNF was added directly to the CFU-GM, BFU-E, and CFU-GEMM colony assays. IL-1 does not appear to function as an intermediary in growth factor production by fibroblasts stimulated with TNF because antibody to IL-1 displayed no effect. Furthermore, assay of TNF-induced fibroblast supernatant was negative for IL-1. These results suggest that TNFα and TNFβ exert both a positive and negative influence on in vitro hemopoietic colony formation.

Original languageEnglish (US)
Pages (from-to)840-844
Number of pages5
JournalJournal of Immunology
Volume140
Issue number3
StatePublished - Jan 1 1988
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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