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

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 α (TNF-α), thromboxane synthase (TXAS, CYP5A), prostacyclin synthase (CYP8A), monocyte chemoattractant protein-1 (MCP-1), peroxisome proliferator-activated receptors (PPAR) α, δ and γ, low-density lipoprotein-associated lipoprotein lipase A2 (LDL-PLA2), apolipoprotein E (apoE) and cholesterol 27-hydroxylase (CYP27). Results. Both TNF-α 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, PPARγ and apoE, provided predictive markers for the development of carotid artery disease within the SSc patient population. Conclusion. The elevated levels of TNF-α 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.