IL-17 Exacerbates Experimental Autoimmune Prostatitis via CXCL1/CXCL2-Mediated Neutrophil Infiltration

Abstract Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. IL-17 is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS remain unclear. Herein, we first confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17 in the prostate of EAP, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased. Treatment of EAP mice with IL-17-neutralizing monoclonal antibody (mAb) resulted in a decreased number of infiltrated neutrophils, as well as the CXCL1 and CXCL2 level. Depletion of neutrophil by anti-Ly6G antibodies ameliorated inflammatory changes and hyperalgesia caused by EAP. Fucoidan, which could potently inhibit neutrophil migration, could also ameliorate the manifestations of EAP. Our finding suggested that IL-17 promoted the production of CXCL1 and CXCL2, which subsequently triggered neutrophil chemotaxis to prostate tissues. And fucoidan might be a potential drug for the therapy of EAP by the effectively inhibiting on neutrophil infiltration.