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Leukemia inhibitory factor is expressed in cartilage and synovium and can contribute to the pathogenesis of arthritis

Academic Article
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Overview

authors

  • Lotz, Martin
  • Moats, T.
  • Villiger, P. M.

publication date

  • September 1992

journal

  • Journal of Clinical Investigation  Journal

abstract

  • This study reports on leukemia inhibitory factor (LIF) in human articular connective tissues. Biologically active LIF is present in synovial fluids from patients with osteoarthritis and at higher titers in samples from patients with rheumatoid arthritis. Cultured human synoviocytes and articular chondrocytes produced biologically active LIF and synthesized and secreted LIF proteins that migrated in SDS PAGE at approximately 43 kD. This was increased after stimulation with IL-1 beta. Chondrocytes in serum-containing cultures expressed the 4.2-kb LIF mRNA. IL-1 beta, LPS, and to a lesser extent tumor necrosis factor-alpha induced LIF gene expression. LIF autoinduced its mRNA and this provides evidence for an effect of this cytokine on function of joint tissue cells. Among a series of growth factors tested, transforming growth factor (TGF beta), including the isoforms TGF-beta1, TGF-beta 2, and TGF-beta 3, platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor induced this cytokine gene but differed with respect to the duration of their effects. Cultured synoviocytes expressed the LIF gene in response to the same set of peptide regulatory factors. Analysis of signal transduction pathways showed that PMA increased LIF mRNA, whereas calcium ionophore and cAMP had no detectable effects. Cycloheximide was a potent LIF mRNA inducer and dexamethasone inhibited LIF induced by PMA or IL-1 beta. Cartilage organ cultures and synovial tissues stimulated with IL-1 expressed high levels of LIF mRNA as demonstrated by in situ hybridization. These results identify LIF as a new cytokine that is produced by joint tissue cells and is overexpressed in arthritis. The induction of this cytokine by factors that are present during joint inflammation and the effects of LIF on connective tissue cells suggest that LIF is a mediator that can contribute to the pathogenesis of arthritis.

subject areas

  • Arthritis
  • Base Sequence
  • Cartilage
  • Cells, Cultured
  • Gene Expression Regulation
  • Growth Inhibitors
  • Humans
  • Interleukin-1
  • Interleukin-6
  • Leukemia Inhibitory Factor
  • Lymphokines
  • Molecular Sequence Data
  • RNA, Messenger
  • Signal Transduction
  • Synovial Membrane
  • Transforming Growth Factor beta
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Research

keywords

  • ARTHRITIS
  • CHONDROCYTES
  • LEUKEMIA INHIBITORY FACTOR
  • SYNOVIOCYTES
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci115964

PubMed ID

  • 1522240
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Additional Document Info

start page

  • 888

end page

  • 896

volume

  • 90

issue

  • 3

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