title: NEFAs activate the oxidative stress-mediated NF-κB signaling pathway to induce inflammatory response in calf hepatocytes.
abstract: Non-esterified fatty acids (NEFAs) are important induction factors of inflammatory responses in some metabolic diseases. High plasma levels of NEFAs and oxidative stress exist in the dairy cows with ketosis. The aim of this study was to investigate whether high levels of NEFAs can induce inflammatory response and the specific molecular mechanism in the hepatocytes of dairy cow. In vitro, primary cultured bovine hepatocytes were treated with different concentrations of NEFAs, PDTC (an NF-κB inhibitor) and NAC (an antioxidant). NEFAs significantly activated NF-κB pathway. Activated NF-κB upregulated the release of pro-inflammatory cytokines, thereby inducing inflammatory response in bovine hepatocytes. When PDTC was added, activation of NF-κB-mediated inflammatory response induced by NEFAs was inhibited. NEFAs treatment results in the overproduction of the markers of oxidative stress, reactive oxygen species (ROS) and malondialdehyde (MDA), which were ameliorated by NAC treatment. These increased ROS and MDA were caused by decreasing activity of antioxidant system, including glutathione peroxidase, superoxide dismutase and catalase, in bovine hepatocytes treated with NEFAs. NAC also ameliorated NEFAs-mediated NF-κB activation and the release of pro-inflammatory cytokines. These results indicate that high concentrations of NEFAs can induce cattle hepatocytes inflammatory response through activating the oxidative stress-mediated NF-κB signaling pathway.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Shi
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Dangdang
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Inner Mongolia National University, Tongliao 028042, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Sun
authors.affiliation: College of Animal Science and Technology, Inner Mongolia National University, Tongliao 028042, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China. Electronic address: lixinwei100@126.com.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China. Electronic address: liuguowen2008@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007662:Ketosis / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005230:Fatty Acids, Nonesterified; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; D010100:Oxygen
keywords: Bovine hepatocytes; Cow ketosis; Inflammatory injury; Non-esterified fatty acids; Oxidative stress