Selenomethionine Inhibits NF-κB-mediated Inflammatory Responses of Bovine Mammary Epithelial Cells Caused by Klebsiella pneumoniae by Increasing Autophagic Flux

  • Biol Trace Elem Res. 2023 Jul 5. doi: 10.1007/s12011-023-03757-2.
Siyan Xu  1  2  3  4 ,  Yixue Miao  1  2  3  4 ,  Junsheng Dong  1  2  3  4 ,  Luying Cui  1  2  3  4 ,  Kangjun Liu  1  2  3  4 ,  Jianji Li  1  2  3  4 ,  Xia Meng  1  2  3 ,  Guoqiang Zhu  1  2  3 ,  Heng Wang  5  6  7  8
Affiliations
  • 1. College of Veterinary Medicine, Yangzhou University, 225009, Yangzhou, China.
  • 2. Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China.
  • 3. International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, Jiangsu, China.
  • 4. Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou, 225009, Jiangsu, China.
  • 5. College of Veterinary Medicine, Yangzhou University, 225009, Yangzhou, China. [email protected].
  • 6. Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. [email protected].
  • 7. International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, 225009, Jiangsu, China. [email protected].
  • 8. Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou, 225009, Jiangsu, China. [email protected].
PMID: 37407885 DOI: 10.1007/s12011-023-03757-2
Abstract

Klebsiella pneumoniae (K. pneumoniae) is one of the major pathogens causing bovine clinical mastitis. Autophagy maintains cellular homeostasis and resists excessive inflammation in eukaryotic organisms. Selenomethionine (Se-Met) is commonly used as a source of selenium supplementation for dairy cows. This study aimed to investigate the effects of Se-Met on inflammatory responses mediated by nuclear factor-kappa B (NF-κB) through Autophagy. We infected bovine mammary epithelial cell line (MAC-T) with K. pneumoniae and examined the expression of autophagy-related proteins and changes in autophagic vesicles, LC3 puncta, and autophagic flux at various intervals. The results showed that K. pneumoniae activated the early-stage Autophagy of MAC-T cells. The levels of LC3-II, Beclin1, and ATG5, as well as the number of LC3 puncta and autophagic vesicles, increased after 2 h post-treatment. However, the late-stage autophagic flux was blocked. Furthermore, the effect of Autophagy on NF-κB-mediated inflammation was investigated with different Autophagy levels. The findings showed that enhanced Autophagy inhibited the K. pneumoniae-induced inflammatory responses of MAC-T cells. The opposite results were found with the inhibition of Autophagy. Finally, we examined the effect of Se-Met on NF-κB-mediated inflammation based on Autophagy. The results indicated that Se-Met alleviated K. pneumoniae-induced autophagic flux blockage, inhibited NF-κB-mediated inflammation, and decreased the adhesion of K. pneumoniae to MAC-T cells. The inhibitory effect of Se-Met on NF-κB-mediated inflammation could be partially blocked by the Autophagy inhibitor chloroquine (CQ). Overall, Se-Met attenuated K. pneumoniae-induced NF-κB-mediated inflammatory responses by enhancing autophagic flux.

Keywords
Autophagy; Bovine mammary epithelial cells; Inflammatory responses; K. pneumoniae; Selenomethionine.
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