Diphenyl pyrimidine exhibits protective effect on Staphylococcus aureus pneumonia in rat model by targeting NLRP3
Wei Duan1, Feizhang Qin2, Dean Wu3
1Department of Clinical Laboratory, First Affiliated Hospital School of Medicine, Shihezi University, Shihezi, Xinjiang, 832008, China.
Abstract:
Pneumonia is one of the most frequent disorder induced by S. aureus infection and accounts for 13.3% of the all the infections caused by staphylococcus. In the present study effect of diphenyl pyrimidine was investigated against Staphylococcus aureus (S. aureus) induced pneumonia in the rat model. The results demonstrated that diphenyl pyrimidine treatment of the rats effectively prevented S. aureus induced increase in mortality in dose-dependent manner. Diphenyl pyrimidine treatment inhibited histopathological changes in S. aureus infected rat lungs. Treatment of the rats with 1.25, 2.5, 5 and 10 mg/kg doses of diphenyl pyrimidine significantly (P < 0.05) reversed S. aureus infection induced increase in interleukin (IL)-1β, IL-18 and tumor necrosis factor (TNF)-α levels. Treatment with 1.25, 2.5, 5 and 10 mg/kg doses of diphenyl pyrimidine significantly (P < 0.05) reversed S. aureus infection induced increase nucleotide-binding domain and leucine-rich repeat containing (NLR) protein (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) and caspase-1 protein expression in rat lungs in dose-dependent manner. The NLRP3, ASC and caspase-1 mRNA level in S. aureus infected rat pulmonary tissues was significantly (P < 0.05) reduced by diphenyl pyrimidine treatment in dose-dependent manner. Thus, diphenyl pyrimidine protects S. aureus-induced pneumonia through suppression of NLRP3 and inflammatory cytokine expression. Therefore, diphenyl pyrimidine can be of therapeutic importance for the treatment of S. aureus induced pneumonia.
Insights
Diphenyl pyrimidine effectively treats Staphylococcus aureus (S. aureus) pneumonia in rats by reducing mortality and lung inflammation. This compound suppresses key inflammatory pathways, including NLRP3, offering therapeutic potential for S. aureus infections.
Area of Science:
- Pharmacology
- Infectious Diseases
- Immunology
Background:
- Staphylococcus aureus (S. aureus) is a frequent cause of pneumonia, accounting for 13.3% of all staphylococcal infections.
- Pneumonia induced by S. aureus leads to increased mortality and significant lung histopathological changes.
- Inflammatory cytokines and the NLRP3 inflammasome pathway are implicated in the pathogenesis of S. aureus pneumonia.
Purpose of the Study:
- To investigate the therapeutic effect of diphenyl pyrimidine against S. aureus-induced pneumonia in a rat model.
- To evaluate the impact of diphenyl pyrimidine on mortality, lung pathology, and inflammatory markers associated with S. aureus pneumonia.
Main Methods:
- Rats were infected with S. aureus to induce pneumonia.
- Diphenyl pyrimidine was administered at various doses (1.25, 2.5, 5, 10 mg/kg) to assess its effects.
- Measurements included mortality rates, lung histopathology, and levels of inflammatory cytokines (IL-1β, IL-18, TNF-α) and inflammasome components (NLRP3, ASC, caspase-1) at protein and mRNA levels.
Main Results:
- Diphenyl pyrimidine significantly reduced S. aureus-induced mortality in a dose-dependent manner.
- Treatment inhibited histopathological damage in infected rat lungs.
- Diphenyl pyrimidine suppressed the elevated levels of IL-1β, IL-18, TNF-α, NLRP3, ASC, and caspase-1 (both protein and mRNA) in a dose-dependent manner.
Conclusions:
- Diphenyl pyrimidine demonstrates protective effects against S. aureus-induced pneumonia in rats.
- The compound exerts its therapeutic action by suppressing the NLRP3 inflammasome pathway and key inflammatory cytokines.
- Diphenyl pyrimidine holds potential as a therapeutic agent for treating S. aureus pneumonia.
