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Updated: May 30, 2025
Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin
Published on: January 17, 2012
Progranulin Plays a Protective Role in Pneumococcal Meningitis by Inhibiting Pyroptosis
Jingyao Wang1,2,3, Lihua Kang1,2,4, Wenlong Xu2
1Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing Medical University, Chongqing, People's Republic of China.
Objective:
Pneumococcal meningitis is a serious infectious disease with a high mortality rate and a global presence, and survivors have different degrees of neurological sequelae as a consequence of the host response to the infection. Progranulin (PGRN) is a multifunctional autocrine growth factor that is also a major immunoregulator. We want to investigate the role for PGRN in Pneumococcal meningitis in vivo and in vitro.
Method:
Mouse and cell models were established to explore the protective effect and mechanism of PGRN against pneumococcal meningitis.
Results:
Progranulin plays a protective role in pneumococcal meningitis by inhibiting pyroptosis. Pyroptosis resulted from exposure of BV-2 cells to the bacterium and this was confirmed in the in vivo model. Administration of the NLRP3 inflammasome inhibitor MCC950 to mice prior to infection inhibited pyroptosis and protected PGRN -/- mice and BV-2 cell model from meningitis.
Conclusion:
This study implicates a protective role for PGRN in pneumococcal meningitis by inhibiting pyroptosis, indicating that PGRN may have therapeutic potential.
Insights
Progranulin (PGRN) protects against pneumococcal meningitis by inhibiting pyroptosis, a cell death pathway. This finding suggests PGRN has therapeutic potential for treating this serious infection.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Pneumococcal meningitis is a severe global infection with high mortality and neurological sequelae.
- Progranulin (PGRN) is an immunoregulatory growth factor with a potential role in host response to infection.
Purpose of the Study:
- To investigate the role of Progranulin (PGRN) in pneumococcal meningitis using in vivo and in vitro models.
- To elucidate the protective mechanisms of PGRN against pneumococcal meningitis.
Main Methods:
- Established mouse and cell (BV-2) models to study pneumococcal meningitis.
- Administered NLRP3 inflammasome inhibitor MCC950 to assess pyroptosis inhibition.
Main Results:
- Progranulin (PGRN) demonstrated a protective effect in pneumococcal meningitis by inhibiting pyroptosis.
- Pyroptosis was observed in BV-2 cells and confirmed in vivo, and its inhibition protected against meningitis.
- MCC950 treatment inhibited pyroptosis and conferred protection in PGRN knockout mice and BV-2 cells.
Conclusions:
- Progranulin (PGRN) plays a protective role in pneumococcal meningitis by suppressing pyroptosis.
- PGRN's mechanism involves the inhibition of the NLRP3 inflammasome pathway.
- PGRN exhibits therapeutic potential for managing pneumococcal meningitis.
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