Toll-like receptor 4 promotes the inflammatory response in septic acute kidney injury by promoting p38 mitogen-activated protein kinase phosphorylation.

Septic acute kidney injury (AKI) contributes to the mortality and morbidity of sepsis patients. Toll-like Receptor 4 (TLR4) has prominent roles in septic AKI. This study investigated the functions of TLR4 in septic AKI. A septic AKI mouse model was established by cecal ligation and puncture surgery. Mouse kidney function and kidney tissue lesion were examined using corresponding kits and H&E staining. The in vitro cell model of septic AKI was established by lipopolysaccharide induction. Cell viability, inflammatory factor (TNF-α, IL-6, IL-4, IL-1β, IL-18) levels, pyroptotic cell number changes, lactate dehydrogenase (LDH) activity, myeloperoxidase (MOP) concentration, and levels of pyroptosis-associated protein and MyD88, TRIF and p38 MAPK phosphorylation were determined by MTT, ELISA, FAM-FLICA Caspase-1 Detection kit, other corresponding kits, and Western blot. TLR4 was highly expressed in septic AKI mouse kidney tissues and human septic AKI cells. TLR4 knockdown alleviated kidney injury, increased cell viability, and reduced LDH activity and MPO concentration. TLR4 knockdown reduced cell pyroptosis by repressing p38 MAPK phosphorylation through MyD88/TRIF, suppressed pro-inflammatory factor (TNF-α, IL-6, IL-4, IL-1β, IL-18) levels, promoted anti-inflammatory factor (IL-4) level, and reduced inflammatory response, thus playing a protective role in septic AKI. Briefly, TLR4 promoted the inflammatory response in septic AKI by promoting p38 MAPK phosphorylation through MyD88/TRIF.