Regulation of Adrenal Aldosterone Production by Serine Protease Prostasin

A serine protease prostasin has been demonstrated to have a pivotal role in the activation of the epithelial sodium channel. Systemic administration of adenovirus carrying human prostasin gene in rats resulted in an increase in plasma prostasin and aldosterone levels. However, the mechanism by which the elevation of prostasin levels in the systemic circulation stimulated the plasma aldosterone levels remains unknown. Therefore, we examined if prostasin increases the aldosterone synthesis in a human adrenocortical cell line (H295R cells). Luciferase assay using CYP11B2 promoter revealed that prostasin significantly increased the transcriptional activity of CYP11B2. Prostasin significantly increased both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner. Surprisingly, treatment with camostat mesilate, a potent prostasin inhibitor, had no effect on the aldosterone synthesis by prostasin and also a protease-dead mutant of prostasin significantly stimulated the aldosterone production. A T-type/L-type calcium channel blocker and a protein kinase C (PKC) inhibitor significantly reduced the aldosterone synthesis by prostasin. Our findings suggest a stimulatory effect of prostasin on the aldosterone synthesis by adrenal gland through the nonproteolytic action and indicate a new role of prostasin in the systemic circulation

Photodynamic Therapy Can Induce a Protective Innate Immune Response against Murine Bacterial Arthritis via Neutrophil Accumulation

Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system. Methodology/Principal Findings: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited. Conclusions/Significance: This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.National Institutes of Health (U.S.) (Grant number R01AI050875

Refractory peritonitis by spontaneous perforation of the common bile duct in a patient receiving peritoneal dialysis

Abstract Background Patients with end-stage renal disease are in an immune-compromised state, with infection being the most common cause of mortality among those undergoing dialysis. Case presentation A 73-year-old woman who had received 6 months of peritoneal dialysis (PD) presented with peritoneal irritation symptoms during hospitalization for examination of PD effluent turbidity. Emergent laparotomy was performed for acute biliary peritonitis, but the cause was undetermined because of severe adhesion, and surgery ended with washing and palliative drainage. Postoperative endoscopic retrograde cholangiopancreatography revealed spontaneous perforation of the common bile duct (CBD), and she was transferred to the intensive care unit (ICU) for treatment of septic shock. Treatment included antibiotics, drainage, mechanical ventilation, and continuous hemodiafiltration, but infection spread into the retroperitoneal tissue and right thigh gradually. On ICU day 53, she died due to multiple organ failure. Conclusions Acute peritonitis due to spontaneous perforation of the CBD is very rare, and to our knowledge, this is the first report of biliary peritonitis in a patient receiving PD. Physicians should pay special attention to refractory peritonitis, including biliary peritonitis, occurring in patients receiving PD because some cases can be fatal

アルドステロン カンレン ジン ショウガイ ニ オケル プラスミン カッセイ ヨクセイ オ カイシタ セリン プロテアーゼ ソガイ ヤク ノ ジン ホゴ コウカ

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