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Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin
Published on: January 17, 2012
Progranulin Protects against Aspergillus fumigatus Keratitis by Attenuating the Inflammatory Response through
Pingli Qi1, Xing Liu1, Cui Li1
1Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Abstract:
Fungal keratitis (FK) is a severe corneal condition caused by pathogenic fungi and is associated with the virulence of fungi and an excessive tissue inflammatory response. Progranulin (PGRN), functioning as a multifunctional growth factor, exerts a pivotal influence on the regulation of inflammation and autophagy. The aim of our research was to analyze the role of PGRN in Aspergillus fumigatus (A. fumigatus) keratitis. We found that PGRN expression was increased in the mouse cornea with A. fumigatus keratitis. In our experiments, corneas of mice with FK were treated with 100 ng/mL of PGRN. In vitro, RAW 264.7 cells were treated with 10 ng/mL of PGRN before A. fumigatus stimulation. The findings suggested that PGRN effectively alleviated corneal edema and decreased the expression of pro-inflammatory cytokines in mice. In stimulated RAW 264.7 cells, PGRN treatment suppressed the expression of pro-inflammatory cytokines IL-6 and TNF-α but promoted the expression of the anti-inflammatory cytokines IL-10. PGRN treatment significantly upregulated the expression of autophagy-related proteins LC3, Beclin-1, and Atg-7. 3-Methyladenine (3-MA, autophagy inhibitor) reversed the regulation of inflammatory cytokines by PGRN. In addition, our study demonstrated that PGRN also enhanced phagocytosis in RAW 264.7 cells. In summary, PGRN attenuated the inflammatory response of A. fumigatus keratitis by increasing autophagy and enhanced the phagocytic activity of RAW 264.7 cells. This showed that PGRN had a protective effect on A. fumigatus keratitis.
Insights
Progranulin (PGRN) reduces inflammation and boosts autophagy in fungal keratitis caused by Aspergillus fumigatus. This study shows PGRN protects the cornea by enhancing immune cell activity and reducing inflammatory responses.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Fungal keratitis (FK) is a severe corneal disease driven by fungal virulence and inflammation.
- Progranulin (PGRN) is a growth factor involved in regulating inflammation and autophagy.
Purpose of the Study:
- To investigate the role of PGRN in Aspergillus fumigatus-induced keratitis.
- To determine PGRN's effects on inflammatory responses and autophagy in FK.
Main Methods:
- Assessed PGRN expression in a mouse model of A. fumigatus keratitis.
- Treated mouse corneas and RAW 264.7 cells with PGRN in vitro.
- Utilized autophagy inhibitor 3-Methyladenine (3-MA) to assess PGRN's mechanism.
Main Results:
- PGRN expression increased in infected corneas.
- PGRN treatment alleviated corneal edema and suppressed pro-inflammatory cytokines (IL-6, TNF-α) while promoting anti-inflammatory IL-10.
- PGRN upregulated autophagy proteins (LC3, Beclin-1, Atg-7) and enhanced phagocytosis.
- Autophagy inhibition reversed PGRN's effects on inflammatory cytokines.
Conclusions:
- PGRN attenuates inflammation in A. fumigatus keratitis by enhancing autophagy and phagocytosis.
- PGRN demonstrates a protective effect against fungal keratitis.
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