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NFκB1/p105 is the critical member of the NFκB family which can suppress inflammation,age-ing,and cancer when p50/p50 homodimer is formed.Currently,the research about the role of NFκB1/p105 during cow mastitis is limited.Here,we analyzed the correlation of six single-nucleotide variants of the NFκB1 gene with somatic cell count,milk yield,milk fat content,and milk protein content in 547 Chinese Holstein cows,and explored the mRNA expression profiles of the NFκB family and ubiquitin ligases(βTrCP1,pTrCP2,KPC1,KPC2)in LPS-induced bovine mam-mary epithelial cells(MECs)by transcriptome-Seq.The association analysis showed that cows with SNV2-TT and SNV6-CC in the NFκB1 gene had significantly higher milk protein content(P＜0.05),while cows with SNV5-TT in the NFκB1 gene had significantly lower somatic cell score(SCS),but CC genotype at SNV5 locus was not detected in our Holstein cows.The transcriptome-Seq results demonstrated the mRNA expression of NFκB1 was increased and peaked at 4 h post-induction,while the mRNA expressions of both KPC1 and BCL3 that promote the anti-inflammation function of NFκB1/p105 were decreased in LPS-induced bovine MECs.TNFAIP3,an inhibitor of both degrada-tion and processing of p105 precursor,was markedly increased by more than 3 folds.Furthermore,bta-miR-125b which targets at the 3'UTR of TNFAIP3 was reduced by 50％.These results indicated that SNV5-TT of the NFκB1 gene with lower SCS may be an anti-mastitis genotype that could cope with infection more efficiently in Chinese Holstein cows.In addition,the anti-inflammation role of NFκB1/p105 seemed to be inhibited in LPS-induced-bovine MECs because the formation of the p50/p50 homodimer was arrested.This study provides a new perspective to understand the inflammatory mechanism in dairy mastitis.