Interleukin-37 protects against acinar cell pyroptosis in acute pancreatitis.

Acute pancreatitis (AP) is a local and/or systemic inflammatory disease that starts with acinar cell injury and necrosis; it has no effective medical treatment and thus remains a life-threatening condition. Interleukin-37 (IL-37), a natural immunomodulator, has demonstrated an antiinflammatory effect; however, the role of IL-37 in AP remains unknown. The serum IL-37 levels of 39 healthy controls and 94 patients with AP were measured. Cholecystokinin was applied to induce pancreatic acinar cell injury in vitro. Classical experimental AP models, such as caerulein, l-arginine, and taurolithocholic acid 3-sulfate disodium salt, were included in the in vivo study. A transgenic mouse model with the IL-37 gene and administration of recombinant IL-37 were used to further investigate the function of IL-37 in AP. Pancreas-specific gasdermin D-knockout (GSDMD-knockout) mice were used to explore the protective mechanism of IL-37. Our results showed that serum IL-37 levels in humans were negatively correlated with the severity of AP. Furthermore, IL-37-transgenic mice and supplementation with recombinant IL-37 could both protect against AP. Mechanistically, IL-37 was able to suppress pyroptosis of injured acinar cells, and specific depletion of GSDMD in the pancreas counteracted the protective effect of IL-37. Our study demonstrates that IL-37 protects against acinar cell pyroptosis in AP.

Naoxintong/PPARα Signaling Inhibits H9c2 Cell Apoptosis and Autophagy in Response to Oxidative Stress.

Naoxintong (NXT) is an empirical formula based on the principle of traditional Chinese medicine, which has been approved by China Food and Drug Administration (CFDA) and is widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. The aim of this study is to investigate the protective mechanism of NXT on H9c2 cells (cardiogenic cell line) in response to H2O2. MTT, Western blot, and flow cytometry (FCM) methods were used to identify the protective effect of NXT extract on H2O2-induced H9c2 cells. Here we found that NXT extract significantly increased H9c2 cell viability and reduced H2O2-induced cell apoptosis and autophagy. More importantly, NXT inhibited H2O2-induced H9c2 cell apoptosis and autophagy by increasing PPARα protein levels. In contrast, silenced PPARα terminated NXT protective effect on H2O2-induced H9c2 cells. These findings suggest that NXT/PPARα signaling suppressed H2O2-induced H9c2 cell apoptosis and autophagy.