The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-alpha- or IL-1beta-stimulated rheumatoid synovial fibroblasts

FEBS Lett. 2000 Jan 7;465(1):23-7. doi: 10.1016/s0014-5793(99)01717-2.


We examined the role of p38 mitogen-activated protein (MAP) kinase in the tumor necrosis factor alpha (TNF-alpha)- or interleukin-1beta (IL-1beta)-induced production of interleukin-6 (IL-6) and interleukin-8 (IL-8) in fresh rheumatoid synovial fibroblast (RSF) cultures concomitantly with the induction of p38 MAP kinase activity. Pretreatment of RSF with a specific p38 MAP kinase inhibitor, SB203580, blocked the induction of IL-6 and IL-8 without affecting nuclear translocation of nuclear factor kappaB (NF-kappaB) or IL-6 and IL-8 mRNA levels. These findings suggest that p38 MAP kinase inhibitor may have synergistic, rather than additive, effect for the treatment of rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Imidazoles / pharmacology*
  • Interleukin-1
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Pyridines / pharmacology*
  • RNA, Messenger / biosynthesis
  • Synovial Membrane / metabolism*
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases


  • Enzyme Inhibitors
  • Imidazoles
  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Pyridines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580