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PMID: 1522240 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 90 ·No. 3 ·1992-09-00 ·Pages 888-96

Lotz M, Moats T, Villiger PM

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.

MeSH Terms
Arthritis/etiology Base Sequence Cartilage/metabolism Cells, Cultured Gene Expression Regulation Growth Inhibitors/analysis,biosynthesis,genetics Humans Interleukin-1/pharmacology Interleukin-6 Leukemia Inhibitory Factor Lymphokines/analysis,biosynthesis,genetics Molecular Sequence Data RNA, Messenger/analysis Signal Transduction Synovial Membrane/chemistry,metabolism Transforming Growth Factor beta/pharmacology
Chemicals
Growth Inhibitors Interleukin-1 Interleukin-6 LIF protein, human Leukemia Inhibitory Factor Lymphokines RNA, Messenger Transforming Growth Factor beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lotz M
Sam and Rose Stein Institute for Research in Aging, University of California, San Diego, La Jolla 92093.
Moats T
Villiger P M
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42 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115964
Published
1992-09-00
Pages
888-96
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC329943
Subset
IM
Grants
NIA NIH HHS · AG07996 · United States
NIAMS NIH HHS · AR39799 · United States
External Links
PubMed source DOI: 10.1172/JCI115964 PMC Full Text View journal details
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