title: High salt primes a specific activation state of macrophages, M(Na).
abstract: High salt is positively associated with the risk of many diseases. However, little is known about the mechanisms. Here we showed that high salt increased proinflammatory molecules, while decreased anti-inflammatory and proendocytic molecules in both human and mouse macrophages. High salt also potentiated lipopolysaccharide-induced macrophage activation and suppressed interleukin 4-induced macrophage activation. High salt induced the proinflammatory aspects by activating p38/cFos and/or Erk1/2/cFos pathways, while inhibited the anti-inflammatory and proendocytic aspects by Erk1/2/signal transducer and activator of transcription 6 pathway. Consistent with the in vitro results, high-salt diet increased proinflammatory gene expression of mouse alveolar macrophages. In mouse models of acute lung injury, high-salt diet aggravated lipopolysaccharide-induced pulmonary macrophage activation and inflammation in lungs. These results identify a novel macrophage activation state, M(Na), and high salt as a potential environmental risk factor for lung inflammation through the induction of M(Na).
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wu-Chang
authors.initials: WC
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lin-Juan
authors.initials: LJ
authors.lastname: Du
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Sun
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhu-Xia
authors.initials: ZX
authors.lastname: Shen
authors.affiliation: Shanghai Key Laboratory of Stomatology, Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Chaoji
authors.initials: C
authors.lastname: Shi
authors.affiliation: Shanghai Key Laboratory of Stomatology, Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Sun
authors.affiliation: Shanghai Key Laboratory of Stomatology, Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Qin
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Jia
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Heng-Yu
authors.initials: HY
authors.lastname: Fan
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yi
authors.affiliation: Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1] Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ 08854, USA [2] Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA [3] Department of Pathology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA [4] Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Lanjing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Sheng-Zhong
authors.initials: SZ
authors.lastname: Duan
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D012965:Sodium Chloride / Q000009:adverse effects*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D012965:Sodium Chloride