TMPRSS2 Affects SIRT1 Expression and NLRP3 Activity and Promotes the Progression of Pneumonia

Abstract

Background: Pneumonia is an inflammatory disease characterized by infection in the lung tissue. Transmembrane Protease Serine 2 (TMPRSS2) is implicated in the onset of inflammatory conditions. However, the precise role of TMPRSS2 in regulating the inflammatory response during pneumonia remains unclear. Hence, this research aims to explore the involvement of TMPRSS2 in pediatric pneumonia and unravel the associated mechanisms. Methods: To induce pneumonia, lipopolysaccharide (LPS) was injected into the lungs of mice, establishing a mouse model of pneumonia. RAW264.7 cells served as an in vitro model for macrophages and underwent a 4-hour LPS stimulation. The expression pattern of TMPRSS2 in the pneumonia model was determined through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. TMPRSS2s impacts on the inflammatory response, lung tissue damage, oxidative stress levels, mitochondrial permeability, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression in pneumonia were assessed through Enzyme-Linked Immunosorbent Assay (ELISA), hematoxylin and eosin (HE) staining, qRT-PCR, and cellular immunofluorescence experiments. The effects of TMPRSS2 knockdown and overexpression on the expression of NLRP3 and Sirtuin 1 (SIRT1) were also investigated using western blotting. Results: The expression of TMPRSS2 mRNA and protein was significantly upregulated in mouse lung tissues upon LPS treatment. TMPRSS2 was found to enhance inflammation and lung damage in mice with pneumonia. Conversely, suppressing TMPRSS2 expression alleviated inflammation and lung damage in mice with pneumonia. Additionally, overexpressing TMPRSS2 intensified the inflammatory response in LPS-stimulated RAW264.7 cells, whereas silencing TMPRSS2 attenuated inflammation. We further demonstrated that TMPRSS2 influences the development of pneumonia by inhibiting SIRT1 expression and inducing NLRP3 activity. Conclusions: Our study suggests that TMPRSS2 promotes the inflammatory progression of pneumonia, and modulates the expression of NLRP3 inflammasome and SIRT1.