Elevated expression of the genes encoding TNF-alpha and thromboxane synthase in leucocytes from patients with systemic sclerosis

Rheumatology (Oxford). 2002 Aug;41(8):869-75. doi: 10.1093/rheumatology/41.8.869.

Abstract

Objective: To determine the expression of molecular markers of prostanoid/fatty acid signalling in leucocytes of patients with systemic sclerosis (SSc).

Methods: Gene expression in patient leucocytes was analysed using real-time fluorescence reverse transcriptase polymerase chain reaction for tumour necrosis factor alpha (TNF-alpha), thromboxane synthase (TXAS, CYP5A), prostacyclin synthase (CYP8A), monocyte chemoattractant protein-1 (MCP-1), peroxisome proliferator-activated receptors (PPAR) alpha, delta and gamma, low-density lipoprotein-associated lipoprotein lipase A(2) (LDL-PLA(2)), apolipoprotein E (apoE) and cholesterol 27-hydroxylase (CYP27).

Results: Both TNF-alpha and TXAS showed an increase in mean expression in the diseased group (6.3-fold and 5.6-fold respectively, P<0.0001). These two markers, along with CYP27, PPARgamma and apoE, provided predictive markers for the development of carotid artery disease within the SSc patient population.

Conclusion: The elevated levels of TNF-alpha and thromboxane seen in SSc patient sera are paralleled by increases in the expression of the appropriate genes in leucocytes. This method will allow us to screen for a large number of candidate markers of disease in order to increase our understanding of the processes underlying the pathology of SSc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Primers
  • Gene Expression Regulation*
  • Genetic Markers
  • Humans
  • Leukocytes / enzymology
  • Leukocytes / immunology*
  • Reference Values
  • Scleroderma, Systemic / enzymology
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology
  • Thromboxane-A Synthase / blood
  • Thromboxane-A Synthase / genetics*
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • DNA Primers
  • Genetic Markers
  • Tumor Necrosis Factor-alpha
  • Thromboxane-A Synthase