Constitutive mRNA and protein production of macrophage colony-stimulating factor but not of other cytokines by synovial fibroblasts from rheumatoid arthritis and osteoarthritis patients

Br J Rheumatol. 1994 Jul;33(7):613-9. doi: 10.1093/rheumatology/33.7.613.

Abstract

This study analyses the mRNA and protein production and their regulation of macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8 and IL-6 by synovial fibroblasts obtained from patients with RA and OA. M-CSF was found to be produced constitutively as opposed to other cytokines. Stimulation of the cells with IL-1 beta caused a marked increase of GM-CSF, IL-8, IL-6 and as well as of M-CSF mRNA levels. In parallel, a time-dependent increase of M-CSF, GM-CSF, IL-8 and IL-6 protein production was observed. Among the cytokine mRNAs examined only that of M-CSF exhibited a pronounced stability in unstimulated synovial fibroblasts, whereas the other cytokines displayed short mRNA half-lives of 1-2 h. Induction by IL-1 beta markedly prolonged IL-8, IL-6 and GM-CSF mRNA half-lives to > 8 h which indicates increased mRNA stability. These findings suggest that among the cytokines that are produced in the inflamed synovium M-CSF may be particularly important for sustaining long-term influx, activation and survival of mononuclear phagocytes. GM-CSF, IL-8 and IL-6, by contrast, may be more involved in more acute cellular responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Cells, Cultured
  • Female
  • Fibroblasts / chemistry
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interleukin-6 / analysis
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / analysis
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Macrophage Colony-Stimulating Factor / analysis
  • Macrophage Colony-Stimulating Factor / genetics*
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Male
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Synovial Membrane / chemistry
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology

Substances

  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor