15-Deoxy-delta12,14-PGJ2, but not troglitazone, modulates IL-1beta effects in human chondrocytes by inhibiting NF-kappaB and AP-1 activation pathways

FEBS Lett. 2001 Jul 13;501(1):24-30. doi: 10.1016/s0014-5793(01)02614-x.

Abstract

The activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to inhibit the production and the effects of proinflammatory cytokines. Since interleukin-1beta (IL-1beta) directly mediates cartilage degradation in osteoarthritis, we investigated the capability of PPARgamma ligands to modulate IL-1beta effects on human chondrocytes. RT-PCR and Western blot analysis revealed that PPARgamma expression was decreased by IL-1beta. 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), in contrast to troglitazone, was highly potent to counteract IL-1beta-induced cyclooxygenase-2 and inductible nitric oxide synthase expression, NO production and the decrease in proteoglycan synthesis. Western blot and gel-shift analyses demonstrated that 15d-PGJ2 inhibited NF-kappaB activation, while troglitazone was ineffective. Although 15d-PGJ2 attenuated activator protein-1 binding on the DNA, it potentiated c-jun migration in the nucleus. The absence or the low effect of troglitazone suggests that 15d-PGJ2 action in human chondrocytes is mainly PPARgamma-independent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Blotting, Western
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chromans / pharmacology*
  • Cyclooxygenase 2
  • DNA / genetics
  • DNA / metabolism
  • Enzyme Induction / drug effects
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / pharmacology*
  • Isoenzymes / genetics
  • Ligands
  • Membrane Proteins
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type II
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandins / biosynthesis
  • Protein Binding / drug effects
  • Proteoglycans / biosynthesis
  • Proto-Oncogene Proteins c-jun / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction / drug effects
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Troglitazone

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Chromans
  • Interleukin-1
  • Isoenzymes
  • Ligands
  • Membrane Proteins
  • NF-kappa B
  • Prostaglandins
  • Proteoglycans
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factor AP-1
  • Transcription Factors
  • Nitric Oxide
  • DNA
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Troglitazone
  • Prostaglandin D2