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

, 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 t...

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Published inInternational journal of molecular sciences Vol. 25; no. 10; p. 5330
Main Authors Yuan, Jianlin, Zhao, Qin, Li, Jinfeng, Wen, Yiping, Wu, Rui, Zhao, Shan, Lang, Yi-Fei, Yan, Qi-Gui, Huang, Xiaobo, Du, Senyan, Cao, San-Jie
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 14.05.2024
Subjects
Animals
Apoptosis
Apoptosis - genetics
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacterial Toxins - genetics
Bacterial Toxins - metabolism
Bacterial Toxins - toxicity
Caspase 8 - genetics
Caspase 8 - metabolism
Cell death
Cell growth
Cell Line
CRISPR-Cas Systems
CXCL8
Cytotoxicity
Gene Knockout Techniques
Genes
Hogs
Interleukin-8 - genetics
Interleukin-8 - metabolism
Kidney diseases
Pasteurella multocida - genetics
Pasteurella multocida toxin
PK15 cells
Proteins
Quality control
Rhinitis
Ribonucleic acid
RNA
Swine
Toxicity
Toxins
Zoonoses
PK15 cells
apoptosis
CXCL8
Pasteurella multocida toxin
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Summary:, 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.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25105330