Abstract
Abstract: :
Purpose: CARD15 is a gene that has recently been identified as a Crohn's disease susceptibility gene at the IBD1 locus, and is the gene responsible for familial juvenile systemic granulomatosis (Blau syndrome). Other autoimmune diseases have been reported to have an association with the IBD1 locus, including systemic lupus erythematosus, multiple sclerosis and ankylosing spondylitis. Patients with all of these diseases may have uveitis. This gene is reported to be expressed only in monocytes. The CARD15 gene encodes a cytoplasmic protein that is capable of activating the NFΚB cell signalling pathway upon stimulation with endotoxin. Therefore we sought to examine potential roles of the CARD15 gene in uveal inflammation. Methods: Human iris endothelial cells (HIEC) and human choroid endothelial cells (HCEC) were stimulated with TNF-α (10 ng/ml), and HIEC were stimulated with endotoxin (10 mg/ml) for up to 24 hours. Cells from stimulated and control cultures were harvested and total RNA was extracted. RT-PCR was utilized to examine expression of the CARD15 gene. Results: In contradiction to prior reports of restricted expression, purified iris and choroid endothelial cells express the CARD15 mRNA. Furthermore, this expression was upregulated at 3 and 24 hours upon stimulation. Conclusion: These results are the first report of CARD15 expression in a cell type other than monocyte. The ocular expression of a gene that controls endotoxin responsiveness has implications for understanding endotoxin-induced uveitis in rodents and granulomatous uveitis in patients.
Keywords: 417 gene/expression • 437 inflammation • 611 uvea