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Elevated expression of the genes encoding TNF-alpha and thromboxane synthase in leucocytes from patients with
1Biomedical Research Centre, Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, UK.
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.