IL-17 Aggravates Experimental Autoimmune Prostatitis Via CXCL1/CXCL2-mediated Neutrophil Infiltration

Research purpose: CP/CPPS is a poorly understood disease and increasing evidence suggests inflammation is involved in the development of CP/CPPS.IL-17 is associated with the occurrence and development of some chronic inflammatory diseases.However,the molecular mechanisms that how IL-17 drive the development of CP/CPPS remain unclear.The aim of this study was to investigate the downstream signaling pathway of IL-17 in experimentalautoimmune prostatitis(EAP).Research methods: EAP model was induced by subcutaneous injecting emulsion of prostate antigens and complete Freund’s adjuvant with NOD mice.Mice were treated with IL-17 neutralization m Ab or isotype Ig G.Afer EAP induction,the pathological appearance of the prostate tissues and chronic pain were assessed.The levels of chemokines were determined by q RT-PCR and ELISA.Neutrophil infiltration into the prostate tissues were detected by FCM and IF.Then,we explored the effect of r IL-17 and fucoidan on prostatic inflammation and chronic pelvic pain in this EAP model Results:Our results suggested that the expression of IL-17 in prostate was paralleled with prostate inflammation and pelvic pain symptoms.Corresponding to the increase of IL-17,the neutrophil infiltration and the level of CXCL1 and CXCL2 were also increased.While the treatment with IL-17-neutralizing m Ab resulted in a reduced number of infiltrated neutrophils,and a significant decrease of CXCL1 and CXCL2.Fucoidan,a competitive inhibitor of selectins needed for neutrophil migration,could partly reverse the effect of recombinant-IL-17(r IL-17)on neutrophil recruitment and hyperalgesia through downregulation of nerve growth factor(NGF)in EAP mice.Conclusion: IL-17 aggravates prostatic inflammation and chronic pelvic pain via CXCL1/CXCL2-mediated neutrophil infiltration in this mouse model of experimental autoimmune prostatitis.The infiltrated neutrophil released algesic mediator,NGF,which locally sensitized the nerve and resulted in hyperalgesia in EAP.