Abstract
BackgroundChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects patient health. Despite the elusiveness of innate therapeutic effects, mesenchymal stromal cells (MSCs) hold great promise for inflammation-related diseases. Recent evidence indicates that disease-specific inflammatory cytokines could enhance the therapeutic effects of MSCs.MethodsBy establishing a CP/CPPS mouse model and pretreating MSCs with the cytokine interleukin-1β (IL-1β), we studied the IL-1β-primed MSC immunoregulatory ability and targeted migration ability in vitro and in CP/CPPS mice.ResultsIL-1β levels significantly increased in the prostate tissue and serum of experimental autoimmune prostatitis (EAP) mice. Pretreatment with IL-1β enhanced the immunomodulatory potential and targeted migration of MSCs in vitro. Furthermore, intravenous infusion of IL-1β-primed MSCs dampened inflammation in prostate tissues and alleviated hyperalgesia in EAP mice. The infused MSCs inhibited monocyte infiltration and promoted regulatory T lymphocyte formation in prostate tissue, thus remodeling the local environment. Surprisingly, IL-1β-primed MSCs exhibited improved accumulation in the spleen but not in prostate tissue. Accordingly, infused MSCs reshaped systemic immunity by reducing the proportion of Ly6ChighCD11b+ monocytes and boosting the proportion of CD4+Foxp3+ regulatory T lymphocytes in the spleen and lung. Inflammatory chemokine (C–C motif) ligand 2 (CCL2) decreased through the downregulation of the NF-κB and JNK/MAPK pathways by inflammatory resolution via MSCs infusion to alleviate pain.ConclusionIn summary, IL-1β-primed MSCs restored systemic immunologic homeostasis to alleviate CP/CPPS by modulating systemic immunity. These findings provide a novel strategy to boost the therapeutic effects of MSC-based therapy for CP/CPPS and reveal the essential role of systematic immunity in the treatment of CP/CPPS with MSC infusion.
Highlights
Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) is a common disorder with chronic pelvic pain, prostatic inflammation, lower urinary tract symptoms, and sexual dysfunction [1, 2]
Through the establishment of a Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) mouse model, we found that the expression of IL-1β was widely increased in the spleen, bloodstream, and prostate
This study found that the inflammatory pathways NF-κB, signal transducer and activator of transcription 3 (STAT3) and MAPK were significantly downregulated via (See figure on page.) Fig. 5 Macrophages changed from a proinflammatory phenotype to an anti-inflammatory phenotype in the prostate
Summary
Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) is a common disorder with chronic pelvic pain, prostatic inflammation, lower urinary tract symptoms, and sexual dysfunction [1, 2]. Recent evidence suggests that immunological disorders are pivotal in the pathophysiological progression of CP/CPPS and other chronic pain syndromes [4,5,6,7]. Clinical trials have demonstrated that anti-inflammatory agents, including cyclooxygenase and corticosteroids, could lead to symptomatic improvement in CP/CPPS patients [9, 10]. Possessing the capacity to rebalance dysregulated immunity, mesenchymal stromal cells (MSCs) have been intensively investigated in various preclinical studies and clinical trials for their translational potential in combating chronic immunological disorders [11]. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects patient health. Despite the elusiveness of innate therapeutic effects, mesenchymal stromal cells (MSCs) hold great promise for inflammationrelated diseases. Recent evidence indicates that disease-specific inflammatory cytokines could enhance the therapeutic effects of MSCs
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