PS6-27. An Increased Immune and Antioxidant Response Indicates Elevated Oxidative Stress In canines with Dermatological Conditions.

Abstract

Dermatitis in canines is a chronic inflammatory condition that is characterized by pruritis, erythema, and alopecia. Inflammation due to an imbalance in oxidative stress (OS), including increased levels of reactive oxygen species (ROS), is implicated in dermatitis. We measured gene expression in leukocytes to identify potential OS and pro-inflammatory signaling pathways in dogs diagnosed with dermatological conditions (n = 18; 3-13.5 yr) and pair-matched healthy dogs (n = 19; 3.5-12.5yr). All dogs were fed a maintenance food for 6 weeks prior to blood collections in RNA PAXgene tubes. This study was approved by IACUC and the Animal Welfare Committee at the Hill’s Pet Nutrition Center. Gene expression from total RNA was measured using the RT2 Profiler PCR array-Dog Oxidative Stress panel of 84 genes and data were analyzed using the ΔΔCt method normalized to RPLP1. There was a significant increase in eosinophil peroxidase (EPX) in derm dogs compared to control (1.5 fold; p < 0.05). This gene contributes to OS and inflammation due to the release of EPX by eosinophils. MGST3, a proinflammatory lipid mediator that recruits eosinophils and leads to ROS formation, was increased in derm dogs (1.28 fold; p < 0.05). There was a modest increase in cytochrome b-245, alpha polypeptide (CYBA) (1.19 fold; ns) and CYBB (1.15 fold; ns), genes that encode for subunits of the NADPH oxidase complex, in derm dogs. NADPH contributes to the formation of superoxides. Interestingly, genes for several antioxidant enzymes including peroxiredoxins were up-regulated in derm dogs including PRDX1 (1.3 fold; p < 0.05), PRDX5 (1.2 fold; p < 0.05), and PRDX6 (1.31 fold; p < 0.05). Peroxiredoxins are known to eliminate hydrogen peroxide and other ROS resulting in the protection of cells. Up-regulation of PRDX1, PRDX5, and PRDX6 may represent a compensatory response to increased OS in derm dogs. PRDX2, however, was down-regulated in derm dogs (-1.36 fold; p < 0.05), and a decrease in this gene may be due to cellular degradation following severe oxidative damage. There was no increase in SOD1 antioxidant enzyme (1.08 fold; ns) but a modest increase in SOD2 (1.39 fold, ns) was seen in derm dogs. Other antioxidant pathways up-regulated in derm dogs include dual specificity phosphatase 1 (DUSP1) (1.75 fold; p < 0.05), sirtuin 2 (SIRT2; 1.36 fold; p < 0.05); serine/threonine-protein kinase 25 (STK25; 1.63 fold; p < 0.05), thioredoxin interacting protein (TXNIP; 1.28 fold; p < 0.05) and thioredoxin reductase 1 (TXNRD1; 1.35 fold; p < 0.05). Taken together, an inflammatory response in leukocytes due to the increase in genes related to eosinophil and potential macrophage production, and along with an increase in antioxidant genes, indicate elevated OS. Nutritional interventions targeting OS-related genes may be beneficial in reducing inflammation and allergic response in dermatitis.