S100A12 promotes inflammation and cell apoptosis in sepsis-induced ARDS via activation of NLRP3 inflammasome signaling.

Sepsis is a multiple organ dysfunction elicited by the dysregulated host immune response to microbial infection. Acute respiratory distress syndrome (ARDS) is a serious and acute inflammatory lung injury resulting from sepsis and other severe diseases. The present study aims to investigate the role of S100A12, a pro-inflammatory factor, in the pathophysiologic mechanism underlying the process in sepsis-induced ARDS. In present study, Hematoxylin and Eosin (H&E) Staining was performed to observe pathological changes. Enzyme-Linked Immunosorbent Assay (ELISA) was employed to analyze the levels of inflammatory cytokines. Western blot, immunohistochemistry (IHC) staining and reverse-transcriptase quantitative real-time PCR (RT-qPCR) were performed to determine target gene and protein expression. TUNEL assay and flow cytometry were performed to assay cell apoptosis. We found that the levels of S100A12 and soluble receptor for advanced glycation end-products (sRAGE) are upregulated in the serum of patients with Sepsis-induced ARDS and sepsis mice. Furthermore, higher cell apoptosis rate was observed in lung tissue of sepsis mice. In addition, S100A12 resulted in excessive mucins and the secretion of inflammatory cytokines secretion, and promoted the expression of chemokines and cell adhesion molecules via activating nucleotide-binding oligomerization domain (Nod) -like receptor (NLR) P3 inflammasome pathway in NHBE cells. Finally, S100A12 increased oxidative stress status and cell apoptosis in NHBE cells. Generally, the present study provides evidence that S100A12 is closely related to pathogenesis of sepsis-induced ARDS. Hence, S100A12 may be a useful biomarker of pulmonary injuries for clinical diagnosis of sepsis-induced ARDS.