| First Author | Liao T | Year | 2006 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 47 |
| Issue | 4 | Pages | 1543-9 |
| PubMed ID | 16565390 | Mgi Jnum | J:108446 |
| Mgi Id | MGI:3624059 | Doi | 10.1167/iovs.05-1238 |
| Citation | Liao T, et al. (2006) Blockade of the interaction of leukotriene b4 with its receptor prevents development of autoimmune uveitis. Invest Ophthalmol Vis Sci 47(4):1543-9 |
| abstractText | PURPOSE: To investigate the role of leukotriene B4 (LTB4) and its receptor BLT1 in the pathogenesis of mouse uveitis. METHODS: Experimental autoimmune uveitis (EAU) was induced in B10RIII mice by immunization of interphotoreceptor retinoid binding protein (IRBP; peptide sequence 161-180) or in C57BL/6 (B6) mice by transfer of activated T cells specific for IRBP1-20. The animals were then treated with and without the BLT1 receptor antagonist, CP105696, at the disease onset after immunization or at day 0 or day 6 after T-cell transfer. EAU was also induced in wild-type B6 (WT) and BLT1-deficient (BLT1-/-) mice by reciprocal transfer of the T cells from B6 to BLT1-deficient mice and vise versa. Clinical signs of inflammation and ocular histology were compared. The chemotactic activity of LTB4 on naive and IRBP-specific autoreactive T cells as well as effector leukocytes was examined. RESULTS: The treatment of CP105696, greatly reduced the intensity of ongoing disease. IRBP1-20-specific T cells derived from wild-type B6 mice induced only mild uveitis in syngeneic BLT1-deficient mice and that IRBP1-20-specific T cells derived from BLT1-/- mice induced milder disease in wild-type B6 mice than those derived from wild-type B6 mice, suggesting that expression of the LTB4 receptor on both activated autoreactive T cells and effector leukocytes was necessary for ocular inflammation to occur. Consistent with these data, transfer of autoreactive T cells from B6 mice to 5-lipoxygenase-deficient (5-LO-/-) mice, which have a functional defect in LTB4 expression, also failed to induce uveitis in the recipient mice. CONCLUSIONS: The results demonstrate a critical role for LTB4 in ocular inflammation and in the development and progression of EAU and suggest a new potential target for therapeutic intervention in this disease. |
