Anti-IL-17 Inhibits PINK1/Parkin Autophagy and M1 Macrophage Polarization in Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is an important and preventable cause of cardiovascular death and disability, but the lack of clarity about its exact mechanisms makes it more difficult to find alternative methods or prevention and treatment. We previously demonstrated that increased IL-17 expression plays a crucial role in the development of RHD-related valvular inflammatory injury. Macrophage autophagy/polarization may be a pro-survival strategy in the initiation and resolution of the inflammatory process. This study investigated the mechanism by which IL-17 regulates autophagy/polarization activation in macrophages. A RHD rat model was generated, and the effects of anti-IL-17 and 3-methyladenine (3-MA) were analyzed. The molecular mechanisms underlying IL-17-induced macrophage autophagy/polarization were investigated via in vitro experiments. In our established RHD rat model, the activation of the macrophage PINK1/Parkin autophagic pathway in valve tissue was accompanied by M1 macrophage infiltration, and anti-IL-17 treatment inhibited autophagy and reversed macrophage inflammatory infiltration, thereby attenuating endothelial-mesenchymal transition (EndMT) in the valve tissue. The efficacy of 3-MA treatment was similar to that of anti-IL-17 treatment. Furthermore, in THP-1 cells, the pharmacological promotion of autophagy by IL-17 induced M1-type polarization, whereas the inhibition of autophagy by 3-MA reversed this process. Mechanistically, silencing PINK1 in THP-1 blocked autophagic flux. Moreover, IL-17-induced M1-polarized macrophages promoted EndMT in HUVECs. This study revealed that IL-17 plays an important role in EndMT in RHD via the PINK1/Parkin autophagic pathway and macrophage polarization, providing a potential therapeutic target.

[Surgical treatment of the old with degenerative lumbar spinal stenosis].

OBJECTIVE: To investigate the perioperative characteristics and surgical methods in treating the old with degenerative lumbar spinal stenosis. METHODS: From January 2000 to October 2007, 36 patients with degenerative lumbar spinal stenosis with the age more than 60 years,including 16 males and 20 females, the age from 60 to 81 years with an average of 67.5 years. Of all patients, 6 cases were treated by simple surgical decompression, 16 cases by decompressive laminectomy, 20 cases by decompressive laminectomy combined with internal fixation and fusion. RESULTS: No death cases occurred during perioperation and complication occurred in 14 cases, including cerebrospinal fluid leakage in 3 cases, incision late healed in 1 case, heart abnormal symptom in 1 case, respiratory infection in 1 case, gastrointestinal symptom in 4 cases, urinary system infection in 1 case, spirital symptom in 1 case. After symptomatic treatment, all complications improved. All the cases were followed up from 6 months to 5 years with an average of 2.5 years. Oswestry scoring improved from preoperative 45.66 +/- 7.12 to postoperative 16.80 +/- 5.75, there was significant difference between before and after operation (P < 0.05). CONCLUSION: The age and heath condition are not operative absolute contraindication in treating old with degenerative lumbar spinal stenosis,with the proper operation modus after controlling concomitant diseases, the surgical treatment could guarantee the satisfactory therapeutic effect.