Deficiency of mindin reduces renal injury after ischemia reperfusion.

BACKGROUND: Acute renal injury (AKI) secondary to ischemia reperfusion (IR) injury continues to be a significant perioperative problem and there is no effective treatment. Mindin belongs to the mindin/F-spondin family and involves in inflammation, proliferation, and cell apoptosis. Previous studies have explored the biological functions of mindin in liver and brain ischemic injury, but its role in AKI is unknown. METHOD: To investigate whether mindin has a pathogenic role, mindin knockout (KO) and wild-type (WT) mice were used to establish renal IR model. After 30 min of ischemia and 24 h of reperfusion, renal histology, serum creatinine, and inflammatory response were examined to assess kidney injury. In vitro, proinflammatory factors and inflammatory signaling pathways were measured in mindin overexpression or knockdown and vector cells after hypoxia/reoxygenation (HR). RESULTS: Following IR, the kidney mindin level was increased in WT mice and deletion of mindin provided significant protection for mice against IR-induced renal injury as manifested by attenuated the elevation of serum creatinine and blood urea nitrogen along with less severity for histological alterations. Mindin deficiency significantly suppressed inflammatory cell infiltration, TNF-α and MCP-1 production following renal IR injury. Mechanistic studies revealed that mindin deficiency inhibits TLR4/JNK/NF-κB signaling activation. In vitro, the expression levels of TNF-α and MCP-1 were increased in mindin overexpression cells compared with vector cells following HR. Moreover, TLR4/JNK/NF-κB signaling activation was elevated in the mindin overexpression cells in response to HR stimulation while mindin knockdown inhibited the activation of TLR4/JNK/ NF-κB signaling after HR in vitro. Further study showed that mindin protein interacted directly with TLR4 protein. And more, mindin protein was confirmed to be expressed massively in renal tubule tissues of human hydronephrosis patients. CONCLUSION: These data demonstrate that mindin is a critical modulator of renal IR injury through regulating inflammatory responses. TLR4/JNK/NF-κB signaling most likely mediates the biological function of mindin in this model of renal ischemia.

[Analysis of cytokines (IL-2, IL-8, IL-10) in the expressed prostatic secretions of chronic prostatitis].

OBJECTIVE: To investigate the levels of immunoregulatory cytokine IL-2, pro-inflammatory cytokine IL-8 and anti-inflammatory cytokine IL-10 in the expressed prostatic secretions (EPS) of chronic prostatitis (CP) patients and to evaluate the significance of the cytokines to the pathogenesis and diagnosis of CP. METHODS: IL-2, IL-8 and IL-10 levels were measured in the EPS of 31 CP patients and 10 normal controls by enzyme-linked immune sandwich assay (ELISA). Urine was cultured and EPS studied according to the 2-glass test. NIH-CPSI (NIH-chronic prostatitis symptom index) was performed in every patient. The cases of CP were divided into 3 types: II (n=5), IIIA (n=13) and IIIB (n=13) according to NIH. RESULTS: The IL-8 levels in CP patients were significantly higher (P < 0.05) while the IL-2 and IL-10 levels significantly lower than those in the controls (both P < 0.05). There was no statistically significant difference between the cytokine levels in II CP and in IIIA CP (P > 0.05). The IL-8 levels in IIIB CP were significantly lower than those in both II CP and IIIA CP (both P < 0.05). The IL-8 levels were correlated directly with WBC count (r = 0.663, P < 0.05) , and inversely with IL-10 levels (r = -0.503, P < 0.05), but there was no correlation between NIH-CPSI scores and cytokines levels (P > 0.05). CONCLUSION: Cytokines may play an important role in pathogenesis of prostatitis. The results indicate that the expression of cytokines (IL-2, IL-8, IL-10) in EPS can serve as a valuable marker for the diagnosis of CP.