title: Hyperlipidemia modifies innate immune responses to lipopolysaccharide via the TLR-NF-κB signaling pathway.
abstract: The objective of this study was to investigate the effect of hyperlipidemia (HLP) on innate immune responses to lipopolysaccharide (LPS). Male New Zealand white rabbits were fed a normal diet (ND) or a high-fat diet (HFD) for 8 weeks. In vivo, the rabbits were injected intravenously with LPS for 24 h. In vitro, peripheral mononuclear cells were collected and stimulated (or unstimulated) with LPS for 24 h. Assay results were analyzed with one-way ANOVA or an equivalent non-parametric test. A P value of 0.05 was considered statistically significant. Despite having no influence in body weight, the HFD intake significantly increased serum lipids, C-reactive protein (CRP), nuclear factor (NF)-κB subunit p65, Toll-like receptor (TLR)-4, SR-A and FAS. Although we found increased circulating tumor necrosis factor (TNF)-α, interleukin (IL)-6, CRP, IL-1β, and IL-10 in the ND-fed rabbits, no significant difference was found in the LPS-stimulated production of TNF-α, IL-6, and CRP in the HFD-fed rabbits. The macrophages harvested from the HFD-fed rabbits developed a blunted inflammatory response, with lower mRNA expression of TNF-α, IL-6, CRP, TLR-4, SR-A, FAS, and Bcl-2 than that expressed by the ND group. In the HFD-fed animals, LPS incubation decreased NF-κB subunit p65 expression, whereas the cytoplasmic phosphorylation of the inhibitor of NF-κB protein was enhanced. These data indicate that HLP displayed a form of innate immune paralysis, including reduced pro- and anti-inflammatory cytokine release to external stimulus, which was related to the altered TLR-NF-κB signaling pathway and altered pro- and anti-apoptotic processes in macrophages.
authors.affiliation: School and Hospital of Stomatology, Fujian Medical University, and Stomatological Key Laboratory of Fujian College and University, Fuzhou, Fujian, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.forename: Gengbing
authors.initials: G
authors.lastname: Lin
authors.forename: Lang
authors.initials: L
authors.lastname: Lei
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: You
authors.forename: Chunfang
authors.initials: C
authors.lastname: Wu
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Fuhua
authors.initials: F
authors.lastname: Yan
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics; D006949:Hyperlipidemias / Q000276:immunology*; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D016328:NF-kappa B / Q000097:blood / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000097:blood / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D019014:fas Receptor / Q000097:blood
chemical_list: D015850:Interleukin-6; D008055:Lipids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D002097:C-Reactive Protein