title: Manganese deficiency or excess caused the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier, as regulated by NF-κB, TOR and Nrf2 signalling, in grass carp (Ctenopharyngodon idella).
abstract: Intestinal mucosal immune components and mRNA levels of inflammatory cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules in young grass carp (Ctenopharyngodon idellus) under dietary manganese (Mn) deficiency or excess were investigated. Fish were fed the diets containing graded levels of Mn [3.65-27.86 mg Mn kg(-1) diet] for 8 weeks. The results demonstrated that Mn deficiency significantly decreased the lysozyme and acid phosphatase (ACP) activities, up-regulated tumour necrosis factor α (TNF-α), interleukin 8 and the signalling factor nuclear factor-κB p65, and down-regulated interleukin 10 (IL-10), transforming growth factor β1, inhibitor of signalling factors κB-α and target of rapamycin mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI). However, Mn deficiency did not change the C3 content in the PI, whereas it decreased the C3 contents in the MI and DI. Additionally, Mn depletion also resulted in significantly low mRNA levels for tight junction proteins (claudin-b, claudin-c, claudin-15, occludin and zonula occludens-1), antioxidant enzymes (MnSOD, GPx and CAT) and NF-E2-related factor-2 in the intestines of fish. Excessive Mn exhibited toxic effects similar to Mn deficiency, where optimal Mn contents reversed those indicators. In conclusion, Mn deficiency or excess causes the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier relating to NF-κB, TOR and Nrf2 signalling in grass carp. Furthermore, quadratic regression analysis at 95% maximum response of lysozyme and acid phosphatase activities in the distal intestine of young grass carp revealed the optimum dietary Mn levels to be 8.90 and 8.99 mg kg(-1) diet, respectively.
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
authors.forename: Wei-Dan
authors.initials: WD
authors.lastname: Jiang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
authors.forename: Ren-Jun
authors.initials: RJ
authors.lastname: Tang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China.
authors.forename: Sheng-Yao
authors.initials: SY
authors.lastname: Kuang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wu
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Zhang
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China.
authors.forename: Wu-Neng
authors.initials: WN
authors.lastname: Tang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China. Electronic address: zhouxq@sicau.edu.cn.
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Zhou
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China. Electronic address: fenglin@sicau.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Feng
mesh_terms: D000135:Acid Phosphatase / Q000276:immunology; D000818:Animals; D002347:Carps; D003176:Complement C3 / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004032:Diet; D029941:Fish Proteins / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008345:Manganese / Q000172:deficiency / Q000276:immunology*; D009113:Muramidase / Q000276:immunology; D051267:NF-E2-Related Factor 2 / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D062725:Tight Junction Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D003176:Complement C3; D016207:Cytokines; D029941:Fish Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D012333:RNA, Messenger; D062725:Tight Junction Proteins; D008345:Manganese; D058570:TOR Serine-Threonine Kinases; D000135:Acid Phosphatase; D009113:Muramidase
keywords: Antioxidant status; Cytokine; Manganese; Nrf2; TOR; Tight junction