Psoriatic inflammation causes hepatic inflammation with concomitant dysregulation in hepatic metabolism via IL-17A/IL-17 receptor signaling in a murine model

Abstract

Psoriatic inflammation has been shown to be associated with cardiovascular dysfunction and systemic inflammation. Recently, psoriasis has also been linked to hepatic disorders, however underlying mechanism connecting the two are unknown. IL-17A being a central pro-inflammatory cytokine in the pathogenesis of psoriasis may be involved in hepatic inflammation through its receptor and downward signaling; however so far no study has investigated IL-17A related signaling in the liver during psoriasis in a murine model. Therefore, this study explored psoriasis-induced hepatic inflammation and concurrent metabolic changes. Mice were applied topically imiquimod (IMQ) to develop psoriatic inflammation. Additionally mice were also treated either with IL-17A or anti-IL17A antibody to explore the role of IL-17 related signaling in liver. Mice were then assessed for hepatic inflammation through assessment of inflammatory/oxidative stress markers (IL-17RC, NFκB, IL-6, MCP-1, IL-1β, GM-CSF, ICAM-1, iNOS, lipid peroxides and myeloperoxidase activity) as well as hepatic injury (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) and protein/lipid metabolic biomarkers (total proteins, albumin, total bilirubin, triglycerides, HDL cholesterol, and total cholesterol). IMQ treatment led to hepatic inflammation as evidenced by increased pro-inflammatory cytokines and oxidative stress with concomitant dysregulation in hepatic protein/lipid metabolism. Treatment with IL-17A further aggravated, whereas treatment with anti-IL17A antibody ameliorated IMQ-induced changes in hepatic injury/inflammation and protein/lipid metabolism. Our study shows for the first time that psoriatic inflammation leads to hepatic inflammation which results in dysregulated protein/lipid metabolism through IL-17RC/NFκB signaling. This could result in increased risk of cardiovascular dysfunction in patients with psoriasis.

Keywords: IL-17 receptor; IL-17A; Liver; Nuclear factor-kappa B; Psoriatic inflammation.