Abstract
Abstract: :
Purpose: To identify the changes in gene expression in experimental autoimmune uveoretinitis (EAU) after systemic treatment of corticosteroid. Methods: C57BL/6 mice were immunized with human interphotoreceptor retinoid–binding protein peptides 1–20 to induce EAU. The peak inflammatory response was observed 16 days after peptide immunization. For gene expressional analysis, two experiments were performed. (Exp1) At peak inflammation, total RNA was extracted and dynamic change of gene expression profiles were obtained by using cDNA microarray which contained most of the cDNAs encoding chemokines/cytokines and their receptors (33 chemokines/21 chemokine receptors, 29 cytokines/34 cytokine receptors). Expression pattern in EAU mice was compared with that in control mice immunized with adjuvants only. (Exp2) EAU mice were treated with single intravenous injection of 7.5mg/kg prednisolone at day16. Eyes were collected at 24, 48 and 72 hours after the treatment. The data comparisons between untreated EAU control and treated samples were performed by using cDNA microarray described above. Results: (Exp 1) Among 117 genes, 37 genes were found to differ by more than 2–fold increase in EAU. Most of these genes were Th1–type chemokines/cytokines and their receptors. There is no gene that showed 2–fold decrease in gene expression. (Exp 2) IL–7 receptor and CCR2 were more than 2–fold down regulated at 24hours after corticosteroid treatment. Many of genes including not only Th1–type chemokines/cytokines and their receptors but also Th2–type ones were gradually suppressed thereafter. Conclusions: These results indicated that Th1–type chemokine/cytokine played a critical role in EAU. It was also indicated that signaling pathways of IL–7 and/or CCR2 might be the main target of corticosteroid in EAU; however, we need further investigations to confirm this.
Keywords: gene microarray • autoimmune disease • cytokines/chemokines