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Knocking down TNFAIP1 alleviates inflammation and oxidative stress in pediatric pneumonia through PI3K/Akt/Nrf2
Jing Chen1, Mengtian Zhao2, Wei Fang1
1Department of Pediatric Cardiovascular Surgery, Anhui Provincial Children's Hospital, Hefei, Anhui, China.
Insights
Tumor necrosis factor alpha-inducible protein 1 (TNFAIP1) negatively regulates pneumonia by reducing inflammation and cell death. This protein may offer a new therapeutic target for treating acute respiratory infections in children.
Area of Science:
- Immunology
- Molecular Biology
- Respiratory Medicine
Background:
- Pneumonia is a significant global health concern, particularly affecting children.
- Investigating the molecular mechanisms of childhood pneumonia is crucial due to increasing incidences.
Purpose of the Study:
- To elucidate the role of tumor necrosis factor alpha-inducible protein 1 (TNFAIP1) in lipopolysaccharide (LPS)-induced pneumonia.
- To analyze the involvement of the PI3K/Akt/Nrf2 pathway in TNFAIP1-mediated lung injury.
Main Methods:
- LPS-induced pneumonia mouse model.
- Assessment of lung function, TNFAIP1 expression, oxidative stress, apoptosis, and inflammation.
- Western blot analysis to investigate the PI3K/Akt/Nrf2 signaling pathway.
Main Results:
- TNFAIP1 expression was elevated in pneumonia but inversely correlated with lung injury.
- Silencing TNFAIP1 reduced inflammation, reactive oxygen species (ROS), and apoptosis.
- The PI3K/Akt/Nrf2 pathway was implicated in TNFAIP1's protective effects.
Conclusions:
- TNFAIP1 acts as a negative regulator in acute pneumonia.
- TNFAIP1 attenuates inflammation, ROS production, and apoptosis via the PI3K/Akt/Nrf2 pathway.
- TNFAIP1 presents a potential therapeutic candidate for pneumonia treatment.
Background:
Pneumonia is an acute respiratory infection with increasing global incidences. Children are more susceptible to pneumonia than adults, and its incidences grow extremely high during peak seasons. Thus, it is necessary to investigate the pathogenesis and molecular mechanism of childhood pneumonia.
Methods:
This study examined the role of tumor necrosis factor alpha-inducible protein 1 (TNFAIP1) in lipopolysaccharide (LPS)-induced pneumonia mice. After LPS exposure, lung function, TNFAIP1 activation, infarction volume, oxidative stress, lung tissue apoptosis ratio, and inflammatory response were assessed by immunohistochemistry staining, hematoxylin and eosin staning, Western blot analysis, terminal deoxynucleotidyl transferase dUTP nick end labelling assay, and enzyme-linked-immunosorbent serologic assay, respectively. The mechanism of TNFAIP1 regulating phosphoinositide 3-kinases (PI3K)-protein kinase B (Akt)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was analyzed by Western blot analysis.
Results:
TNFAIP1 expression was enhanced in the LPS-induced pneumonia mice but was negatively correlated with the LPS-induced lung injury. Silencing TNFAIP1 alleviated inflammatory response, production of reactive oxygen species (ROS), and cellular apoptosis in LPS-induced pneumonia. Moreover, PI3K/Akt/Nrf2 signaling pathways were predominantly involved in the TNFAIP1-mediated lung injury, which also played a role in the process of LPS-induced pneumonia.
Conclusion:
This study suggested that TNFAIP1 acted as a negative regulator of acute pneumonia by attenuating inflammatory response, production of ROS, and cellular apoptosis via PI3K/Akt/Nrf2 pathway. The findings suggested that TNFAIP1 is a potential candidate for pneumonia therapy.
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