Abstract
Purpose: :
Inhibition of ERK MAPK suppresses IL-23- and IL-1-driven IL-17 production and attenuates autoimmune disease. We investigated effect of an ERK inhibitor (PD98059) on experimental autoimmunue uveoretinitis (EAU).
Methods: :
C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein (IRBP) peptide, and the severity of EAU disease was scored. The ERK inhibitor (20mg/kg/day) was administered i.p. every two days from day 0 postimmunization. The histological scores were evaluated on day 14 postimmunization. Lymphocyte proliferation was measured by [3H]thymidine incorporation into antigen-stimulated T cells.
Results: :
Histological scores of EAU were decreased in the ERK inhibitor-treated groups. Lymphocyte proliferation assay demonstrated decreased proliferation in the presence of IRBP-Ag in the ERK inhibitor-treated groups, compared with controls.
Conclusions: :
The ERK inhibitor exhibited significant anti-inflammatory and immunosuppressive effects in EAU. The ERK inhibitor may be a promising therapeutic modality for autoimmune uveitis.
Keywords: uveitis-clinical/animal model • autoimmune disease • signal transduction: pharmacology/physiology