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


CONCLUSIONS
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.
Young
V
V
Biomedical Research Centre, Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, UK.
Ho
M
M
Vosper
H
H
Belch
J J F
JJ
Palmer
C N A
CN
D001483:Base Sequence; D017931:DNA Primers; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D007962:Leukocytes / Q000201:enzymology / Q000276:immunology*; D012016:Reference Values; D012595:Scleroderma, Systemic / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D013930:Thromboxane-A Synthase / Q000097:blood / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017931:DNA Primers; D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha; D013930:Thromboxane-A Synthase