AUTHOR=Zhang Hefei , Zheng Jiasan , Sun Yue , Yang Chunxue , Yue Yang 

TITLE=NF-κB signaling pathway mechanism in cow intertoe skin inflammation caused by Fusobacterium necrophorum

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1156449

DOI=10.3389/fcimb.2023.1156449

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p><italic>Fusobacterium necrophorum</italic> is the main pathogen inducing bovine foot rot. The infected site is often accompanied by a strong inflammatory response, but the specific inflammatory regulatory mechanism remains unclear.</p></sec><sec><title>Aim</title><p>A cow skin explants model was established to elucidate the mechanism of <italic>F. necrophorum</italic> bacillus causing foot rot in cows, and to provide reference for future clinical practice.</p></sec><sec><title>Methods</title><p>Cow intertoe skin explants were cultured <italic>in vitro</italic>, and <italic>F. necrophorum</italic> bacteria solution and nuclear factor-κB (NF-κB) inhibitor BAY 1-7082 were added to establish an <italic>in vitro</italic> infection model. Hematoxylin and eosin staining, terminal - deoxynucleotidyl transferase mediated nick end labeling, and immunohistochemistry were used to detect the pathological changes of the skin explants infected with <italic>F. necrophorum</italic>, the degree of tissue cell apoptosis, and the expression of the apoptosis-related protein Caspase-3, respectively. RT-qPCR, Western blot, and ELISA were used to detect the activation of the NF-κB pathway and inflammatory cytokines by <italic>F. necrophorum</italic>.</p></sec><sec><title>Results</title><p>The intertoe skin structure of cows infected with <italic>F. necrophorum</italic> changed with different degrees of inflammation, and the degree of tissue cell apoptosis was significantly increased (<italic>P</italic> &lt; 0.01). In addition, infection with <italic>F. necrophorum</italic> significantly increased the phosphorylation level of IκBα protein and up-regulated the expression level of NF-κB p65. The high expression and transcriptional activity of NF-κB p65 significantly increased the expression and concentration of the inflammatory cytokines TNF-α, IL-1β, and IL-8, thus inducing the occurrence of an inflammatory response. However, inhibition of NF-κB p65 activity significantly decreased the expression of inflammatory factors in the intertoe skin of cows infected with <italic>F. necrophorum</italic>.</p></sec><sec><title>Conclusion</title><p><italic>F. necrophorum</italic> activates NF‐κB signaling pathway by increasing the expression of TNF‐α, IL‐1β, IL‐8 and other inflammatory factors, leading to foot rot in dairy cows.</p></sec>