Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice

Abstract

Background

Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled.

Methods

To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit.

Results

Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy.

Conclusion

The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.

Keywords:

• Pulmonary emphysema
• GBP5
• ARDS
• autophagy
• inflammation

Acknowledgment

The authors would like to thank all the participants who contributed to this study. We also thank the technical support provided by the laboratory staff.

Disclosure statement

The authors declare no conflict of interest.

Ethical approval

Animal attending was performed following the guidelines of the Animal Committee of The First People’s Hospital of Chenzhou.

Data availability statement

All data generated or analyzed during this study are included in this published article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.