Inflammatory arthritis is significantly attenuated in alox15 -/- mice 3900

Abstract Description Rheumatoid arthritis (RA) is a chronic inflammatory disease. 12/15-Lipoxygenase (LO), coded by the alox15 gene, catalyzes the biosynthesis of some lipid mediators of inflammation, however, it’s involvement in pro-inflammatory or pro-resolution pathways in RA is poorly studied. Here we investigated inflammatory arthritis in wild-type and alox15-/- mice. Methods. Inflammatory arthritis was induced in alox15 +/+ and alox15 -/- mice using the K/BxN serum transfer model. Joint inflammation was measured using clinical index and ankle thickness measurements daily and locomotor activity was measured using SmartCagesTM. Lipid mediators (LC-MS/MS) and cytokines and chemokines (flow cytometry using LEGENDplex™ panels) were measured in joint tissue homogenates. Histopathology of joints was measured by H&E staining. Results. Inflammation scores in Alox15 +/+ mice were strikingly greater compared to Alox15 -/- mice (p < 0.01, RM-ANOVA), and alox15 +/+ mice had significantly reduced locomotor activity. Histopathology showed significantly reduced infiltration of inflammatory cells alox15 -/- mice. Concentrations of several cytokines and chemokines were significantly lower in joints of alox15 -/- mice. Discussion. Planned analyses of lipid mediators in inflamed joints will provide additional mechanistic information. Together, these data demonstrate that 12/15-LO is implicated in the severity of inflammatory arthritis and may be a therapeutic target for inflammatory arthritis. Funding Sources Supported by the Canadian Institutes for Health Research (CIHR) grant #165965. Topic Categories Immune Mechanisms of Human Disease (HUM)