title: Protective effects of melatonin on lipopolysaccharide-induced mastitis in mice.
abstract: Melatonin, a secretory product of the pineal gland, has been reported to have antioxidant and anti-inflammatory effects. However, the protective effects of melatonin on lipopolysaccharide (LPS)-induced mastitis have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of melatonin on LPS-induced mastitis both in vivo and in vitro. In vivo, our results showed that melatonin attenuated LPS-induced mammary histopathologic changes and myeloperoxidase (MPO) activity. Melatonin also inhibited LPS-induced inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in mammary tissues. In vitro, melatonin was found to inhibit LPS-induced TNF-α and IL-6 production in mouse mammary epithelial cells. Melatonin also suppressed LPS-induced Toll-like receptor 4 (TLR4) expression and nuclear factor-kappaB (NF-κB) activation in a dose-dependent manner. In addition, melatonin was found to up-regulate the expression of PPAR-γ. Inhibition of PPAR-γ by GW9662 reduced the anti-inflammatory effects of melatonin. In conclusion, we found that melatonin, for the first time, had protective effects on LPS-induced mastitis in mice. The anti-inflammatory mechanism of melatonin was through activating PPAR-γ which subsequently inhibited LPS-induced inflammatory responses.
authors.affiliation: The Second Hospital of Jilin University, China.
authors.forename: Guoxi
authors.initials: G
authors.lastname: Shao
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, 235 East Nanjing Road, Nanchang 330047, China.
authors.forename: Yinggang
authors.initials: Y
authors.lastname: Tian
authors.affiliation: College of Veterinary Medicine, Jilin University, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Jilin University, China.
authors.forename: Fangning
authors.initials: F
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, China. Electronic address: xiegh@jlu.edu.cn.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Xie
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008321:Mammary Glands, Animal / Q000473:pathology; D008413:Mastitis / Q000139:chemically induced / Q000517:prevention & control*; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics; D009195:Peroxidase / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D013778:Tetrazolium Salts; D013844:Thiazoles; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009195:Peroxidase; C022616:thiazolyl blue; D008550:Melatonin
keywords: LPS; Mastitis; Melatonin; NF-κB; PPAR-γ