Opening Tight Junctions may be Key to Opening the Blood-Prostate Barrier

Shang, Yangyang; Dong, Chao; Yi, Shanhong

doi:10.12659/msm.890902

Cited by 12 publications

(4 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Few drugs are able to reach the prostatic ducts or acini via the systemic circulation, due to the existence of a blood-prostate barrier activity preventing the distribution of a number of chemicals, including antibacterial agents, to the various cells and regions within the gland ( 30 ).…”

Section: Resultsmentioning

confidence: 99%

Aminoglycoside antibiotics for NIH category II chronic bacterial prostatitis: A single-cohort study with one-year follow-up

Magri

Montanari

Marras

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Although fluoroquinolones are first-line agents for the treatment of National Institutes of Health (NIH) category II chronic bacterial prostatitis (CBP), therapy with these agents is not always feasible due to the increasing worldwide resistance of causative uropathogens. New therapeutic options are urgently required, as drugs such as β-lactam antibiotics distribute poorly to prostatic sites of infection and trimethoprim therapy is often unfeasible due to high resistance rates. The present study aimed to analyze the efficacy of aminoglycosides, administered to a cohort of 78 patients affected by fluoroquinolone-resistant CBP, or excluded from fluoroquinolone therapy due to various contraindications. Patients received netilmicin (4.5 mg/kg, once-daily, intramuscular), combined or not with a β-lactam antibiotic, for 4 weeks. Follow-up visits were scheduled 6 and 12 months after the end of treatment. Fifty-five out of 70 patients (78.6%) showed eradication of the causative pathogen, and a significant reduction of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) total score from a baseline median value of 21 to 14 at the end of therapy, and to 9 and 8 at 6-month and 12-month follow-up assessments, respectively. The pain, voiding and quality of life subdomains of the NIH-CPSI decreased accordingly. In 15 patients showing persistence of infection, NIH-CPSI total and subdomain scores did not decrease at the end of therapy. Additional clinical parameters, such as the urinary peak flow rate, percentage voided bladder, serum prostate-specific antigen concentration, International Prostate Symptom Score and prostate volume improved significantly only in the group of patients in which the infection was eradicated. Therapy was well tolerated, and genetic testing for deafness-predisposing mitochondrial mutations allowed safer administration of aminoglycosides. These results suggest that aminoglycosides may become a therapeutic alternative for the treatment of CBP. These findings should be further validated in a randomized-controlled setting.

show abstract

Section: Resultsmentioning

confidence: 99%

Aminoglycoside antibiotics for NIH category II chronic bacterial prostatitis: A single-cohort study with one-year follow-up

Magri

Montanari

Marras

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…The blood–brain barrier-specific antigen EBA is also expressed in the prostate [ 84 , 85 ]. The prostate and blood vessels have a barrier similar to the blood–brain and blood-testis barriers [ 85 , 86 ]. Because capillary endothelial cells have special structures and functions, the final concentration of drugs and other therapeutic substances is lower in local tissue than in the bloodstream [ 87 ].…”

Section: Discussionmentioning

confidence: 99%

IL-1β-primed mesenchymal stromal cells exert enhanced therapeutic effects to alleviate Chronic Prostatitis/Chronic Pelvic Pain Syndrome through systemic immunity

et al. 2021

View full text Add to dashboard Cite

Background 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 inflammation-related diseases. Recent evidence indicates that disease-specific inflammatory cytokines could enhance the therapeutic effects of MSCs. Methods By 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. Results IL-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. Conclusion In 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.

show abstract

“…However, our results indicated that BMMSC alone treatment did not seem to exert a favorable anti-inflammatory effect in the CBP model. This may be due to the blood-prostate barrier preventing the efficient accumulation of BMMSCs into the prostate tissue [ 31 ]. Importantly, in our CBP model, we discovered that DHA treatment promoted the accumulation of BMMSCs into the prostate tissue in a concentration-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Promoted Bone Marrow Mesenchymal Stem Cell Homing and Suppressed Inflammation and Oxidative Stress against Prostate Injury in Chronic Bacterial Prostatitis Mice Model

Shen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Although bone marrow mesenchymal stem cells (BMMSCs) are effective in treating chronic bacterial prostatitis (CBP), the homing of BMMSCs seems to require ultrasound induction. Dihydroartemisinin (DHA) is an important derivative of artemisinin (ART) and has been previously reported to alleviate inflammation and autoimmune diseases. But the effect of DHA on chronic prostatitis (CP) is still unclear. This study aims to clarify the efficacy and mechanism of DHA in the treatment of CBP and its effect on the accumulation of BMMSCs. The experimental CBP was produced in C57BL/6 male mice via intraurethrally administered E. coli solution. Results showed that DHA treatment concentration-dependently promoted the accumulation of BMMSCs in prostate tissue of CBP mice. In addition, DHA and BMMSCs cotreatment significantly alleviated inflammation and improved prostate damage by decreasing the expression of proinflammatory factors such as TNF-α, IL-1β, and chemokines CXCL2, CXCL9, CXCL10, and CXCL11 in prostate tissue of CBP mice. Moreover, DHA and BMMSCs cotreatment displayed antioxidation property by increasing the production of glutathione peroxidase (GSH-Px), SOD, and decreasing malondialdehyde (MDA) expression. Mechanically, DHA and BMMSCs cotreatment significantly inhibited the expression of TGFβ-RI, TGFβ-RII, phosphor (p)-Smad2/3, and Smad4 in a dose-dependent manner while stimulated Smad7 expression in the same manner. In conclusion, our findings provided evidence that DHA effectively eliminated inflammatory and oxidative stress against prostate injury, and this effect involved the TGF-β/Smad signaling pathway in CBP.

show abstract

Opening Tight Junctions may be Key to Opening the Blood-Prostate Barrier

Cited by 12 publications

References 24 publications

Aminoglycoside antibiotics for NIH category II chronic bacterial prostatitis: A single-cohort study with one-year follow-up

Aminoglycoside antibiotics for NIH category II chronic bacterial prostatitis: A single-cohort study with one-year follow-up

IL-1β-primed mesenchymal stromal cells exert enhanced therapeutic effects to alleviate Chronic Prostatitis/Chronic Pelvic Pain Syndrome through systemic immunity

Dihydroartemisinin Promoted Bone Marrow Mesenchymal Stem Cell Homing and Suppressed Inflammation and Oxidative Stress against Prostate Injury in Chronic Bacterial Prostatitis Mice Model

Contact Info

Product

Resources

About