Pathogenic Roles of CXCL10 in Experimental Autoimmune Prostatitis by Modulating Macrophage Chemotaxis and Cytokine Secretion

Abstract

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is an inflammatory immune disease characterized by intraprostatic leukocyte infiltration and pelvic or perineal pain. Macrophages play vital roles in the pathogenesis of CP/CPPS. However, the mechanisms controlling the activation and chemotaxis of macrophages in CP/CPPS remain unclear. This study aimed to investigate the roles of the CXCL10/CXCR3 pathway in the activation and chemotaxis of macrophages in CP/CPPS patients. The serums of CP/CPPS patients and healthy volunteers were collected and measured. Results showed that CXCL10 expression was significantly elevated and correlated with the severity of CP/CPPS patients. The experimental autoimmune prostatitis (EAP) model was generated, and adeno-associated virus and CXCR3 inhibitors were used to treat EAP mice. Immunofluorescence, flow cytometry, and Western blotting were used to analyze the functional phenotype and regulation mechanism of macrophages. Results showed that CXCL10 deficiency ameliorates EAP severity by inhibiting infiltration of macrophages to prostate. Moreover, CXCL10 could induce macrophage migrations and secretions of proinflammatory mediators via CXCR3, which consequently activated the downstream Erk1/2 and p38 MAPK signaling pathways. We also showed that prostatic stromal cell is a potential source of CXCL10. Our results indicated CXCL10 as an important mediator involved in inflammatory infiltration and pain symptoms of prostatitis by promoting the migration of macrophages and secretion of inflammatory mediators via CXCR3-mediated ERK and p38 MAPK activation.

Paeonol Ameliorates Chronic Itch and Spinal Astrocytic Activation via CXCR3 in an Experimental Dry Skin Model in Mice

“…CXCR3 signaling has been reported involving in various human diseases, including chronic inflammation, immune dysfunction, cancer, metastasis, and pruritus (Van Raemdonck et al, 2015). CXCR3/CXCL10 axis contributes to the recruitment of inflammatory cells and the production of cytokines in RA progression (Lee et al, 2017), chronic prostatitis (Hua et al, 2021), inflammatory bowel disease (Zhao et al, 2017), etc. In addtion to its traditional functions in inflammation and immunity as we known, the potential role of CXCR3 in chronic dermatitis on itch sensation has attracted growing attention in recent years.…”

Efficacy of acupuncture for chronic prostatitis/chronic pelvic pain syndromes on quality of life: study protocol for a randomized, sham acupuncture-controlled trial

“…Many factors, such as urinary reflux [17] , pathogen infection [18] , inflammation, and oxidative stress [19,20] , may be involved in the pathogenesis of CP/CPPS. However, the existing treatment methods are not ideal because of their complicated clinical manifestations and lingering disease [21] .…”

“…Therefore, we assume that true acupuncture will have better clinical efficacy than sham acupuncture in improving QoL, symptom score, and long-term effectiveness. [12][13][14][15][16][17][18][19][20]. A total of 70 patients will be recruited, and all patients enrolled in the trial will voluntarily sign the informed consent form.…”

High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma

“…Cells and tissues were homogenized and lysed with ice-cold RIPA buffer supplemented with a proteasome and phosphatase inhibitor (#P0013B, Beyotime, China) for 30 min, and total proteins were extracted. The procedure for standard western blotting was performed as described in a previous study [ 23 ]. Primary antibodies anti-GAPDH (1:1000, #2118; CST) and anti-HAMP (1:1000, BM5068; Boster) were used to determine the expression of the corresponding proteins.…”