Polydatin alleviates mycoplasma pneumoniae-induced injury via inhibition of Caspase-1/GSDMD-dependent pyroptosis

Yiliu Chen; Yonghong Jiang; Xiuxiu Liu; Xiufeng Chen; Qiuyue Fan; Zhen Xiao

doi:10.1016/j.ijmm.2023.151586

Polydatin alleviates mycoplasma pneumoniae-induced injury via inhibition of Caspase-1/GSDMD-dependent pyroptosis

Int J Med Microbiol. 2023 Sep;313(5):151586. doi: 10.1016/j.ijmm.2023.151586. Epub 2023 Sep 26.

Authors

Yiliu Chen¹, Yonghong Jiang², Xiuxiu Liu³, Xiufeng Chen⁴, Qiuyue Fan⁵, Zhen Xiao⁶

Affiliations

¹ Department of Pediatric, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: chenyl0322@163.com.
² Department of Pediatric, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: jyh203225@126.com.
³ Department of Pediatric, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: liuxiuxiu@shutcm.edu.cn.
⁴ Department of Pediatric, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: chenxiufeng91@163.com.
⁵ Department of Pediatric, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: 17803850740@163.com.
⁶ Department of Pediatric, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: Xiaozhen@shutcm.edu.cn.

PMID: 37776814
DOI: 10.1016/j.ijmm.2023.151586

Abstract

Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1β (IL-1β) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS-2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inﬂammation.

Keywords: Epithelial pyroptosis; GSDMD; MP; Pneumonia; Polydatin.

MeSH terms

Animals
Caspase 1 / metabolism
Child
Gasdermins
Humans
Intracellular Signaling Peptides and Proteins
Mice
Mycoplasma pneumoniae*
Phosphate-Binding Proteins / metabolism
Pneumonia, Mycoplasma* / drug therapy
Pore Forming Cytotoxic Proteins / metabolism
Pyroptosis

Substances

Caspase 1
polydatin
Intracellular Signaling Peptides and Proteins
Gasdermins
GSDMD protein, human
Phosphate-Binding Proteins
Pore Forming Cytotoxic Proteins