CXCL8 Knockout: A Key to Resisting Pasteurella multocida Toxin-Induced Cytotoxicity

Autor: Jianlin Yuan, Qin Zhao, Jinfeng Li, Yiping Wen, Rui Wu, Shan Zhao, Yi-Fei Lang, Qi-Gui Yan, Xiaobo Huang, Senyan Du, San-Jie Cao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 25, Iss 10, p 5330 (2024)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
19325142
DOI: 10.3390/ijms25105330
Popis: Pasteurella multocida, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its mechanism of cytotoxicity remains unclear. In this study, we expressed PMT, purified it in a prokaryotic expression system, and found that it killed PK15 cells. The host factor CXCL8 was significantly upregulated among the differentially expressed genes in a transcriptome sequencing analysis and qPCR verification. We constructed a CXCL8-knockout cell line with a CRISPR/Cas9 system and found that CXCL8 knockout significantly increased resistance to PMT-induced cell apoptosis. CXCL8 knockout impaired the cleavage efficiency of apoptosis-related proteins, including Caspase3, Caspase8, and PARP1, as demonstrated with Western blot. In conclusion, these findings establish that CXCL8 facilitates PMT-induced PK15 cell death, which involves apoptotic pathways; this observation documents that CXCL8 plays a key role in PMT-induced PK15 cell death.
Databáze: Directory of Open Access Journals
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