Expression of TNF-alpha and related signaling molecules in the peripheral blood mononuclear cells of rheumatoid arthritis patients

Mediators Inflamm. 2006;2006(3):12682. doi: 10.1155/MI/2006/12682.

Abstract

We examined the role of tumor necrosis factor (TNF-alpha) and its related signaling intermediates leading to apoptosis/proliferation in the peripheral blood mononuclear cells (PBMCs) of RA patients. The constitutive expression of mRNA for TNF-alpha receptors (TNFR-I and TNFR-II) and the adapter molecules, such as the TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor interacting protein (RIP), and TNF receptor-associated factor 2 (TRAF-2) were analyzed by reverse transcriptase-PCR (RT-PCR) in PBMCs from control and RA cases. PBMCs of RA patients showed a significant increase in TNF-alpha and TNFR-I expression as compared with that from control subjects along with significantly increased constitutive expression of TRADD, RIP, and TRAF-2 mRNA. There was a decrease in expression of FADD in RA patients, but the difference was not significant as compared to controls. These data suggested enhanced signaling by the TNFR-I-TRADD-RIP-TRAF-2 pathway and suppressed signaling by the TNFR-I-TRADD-FADD pathway in PBMCs of RA patients. However, the regulatory mechanisms for TNF-alpha induced signaling may not be explained only by these pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology
  • Arthritis, Rheumatoid / immunology*
  • Fas-Associated Death Domain Protein
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type I / physiology
  • Receptors, Tumor Necrosis Factor, Type II / genetics
  • Receptors, Tumor Necrosis Factor, Type II / physiology
  • Signal Transduction / physiology*
  • TNF Receptor-Associated Factor 2 / genetics
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / physiology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Tumor Necrosis Factor-alpha
  • Protein Serine-Threonine Kinases
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases