title: Atherogenic high cholesterol/high fat diet induces TLRs-associated pulmonary inflammation in C57BL/6J mice.
abstract: OBJECTIVE
  To explore the effects of high cholesterol/high fat diet-induced hypercholesterolemia on pulmonary homeostasis of wild-type C57BL/6J mice.
  
  
  METHODS
  Six- to eight-week-old male C57BL/6J mice were randomly divided into two groups and treated with either high cholesterol/high fat diet (HCD, containing 20 % fat, 1.25 % cholesterol and 0.5 % sodium cholate) or a matching regular diet (RD, containing 4 % fat with no cholesterol and cholate added) for 12-16 weeks.
  
  
  RESULTS
  Twelve to sixteen weeks after HCD diet feeding, hypercholesterolemia and pulmonary lipid accumulation were progressively exacerbated in C57BL/6J mice. Meanwhile, the HCD-fed mice showed distinctive signs of inflammation in the lung, which includes macrophage accumulation in alveolar lumen and lymphocyte infiltration around perivascular area. Simultaneously, the mRNA and protein expression of TLR2 and TLR4 were significantly up-regulated, and the translocation of NFκB into nucleus was activated in HCD-fed mice lung. In vitro, oxidized low-density lipoprotein (oxLDL) could directly up-regulate the expression of TLR2 and TLR4 in both A549 and MLE-12 lung epithelial cell lines.
  
  
  CONCLUSIONS
  These findings suggested that high cholesterol/high fat diet-induced hypercholesterolemia could result in TLRs/NFκB pathway-associated low-grade pulmonary inflammation in C57BL/6J mice, which might alter the lung's immune responsiveness to a variety of environmental exposures.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.|Key Laboratory of Molecular Biology on Infectious Diseases, Center for Lipid Research, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.|Department of Clinical Nutrition, Taizhou Hospital, Linhai, 317000, Zhejiang Province, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China. xuemeilian@cqmu.edu.cn.|Key Laboratory of Molecular Biology on Infectious Diseases, Center for Lipid Research, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. xuemeilian@cqmu.edu.cn.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Lian
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D002791:Cholesterol, Dietary; D059305:Diet, High-Fat; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D002791:Cholesterol, Dietary; D016328:NF-kappa B; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: Atherogenic diet; Hypercholesterolemia; Pulmonary inflammation; Toll-like receptors