title: Hyperlipidemia impaired innate immune response to periodontal pathogen porphyromonas gingivalis in apolipoprotein E knockout mice.
abstract: A finely-tuned innate immune response plays a pivotal role in protecting host against bacterial invasion during periodontal disease progression. Hyperlipidemia has been suggested to exacerbate periodontal health condition. However, the underlying mechanism has not been addressed. In the present study, we investigated the effect of hyperlipidemia on innate immune responses to periodontal pathogen Porphyromonas gingivalis infection. Apolipoprotein E-deficient and wild-type mice at the age of 20 weeks were used for the study. Peritoneal macrophages were isolated and subsequently used for the study of viable P. gingivalis infection. ApoE(-/-) mice demonstrated inhibited iNOS production and impaired clearance of P. gingivalis in vitro and in vivo; furthermore, ApoE(-/-) mice displayed disrupted cytokine production pattern in response to P. gingivalis, with a decreased production of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β and monocyte chemotactic protein-1. Microarray data demonstrated that Toll-like receptor (TLR) and NOD-like receptor (NLR) pathway were altered in ApoE(-/-) mice macrophages; further analysis of pattern recognition receptors (PRRs) demonstrated that expression of triggering receptors on myeloid cells-1 (TREM-1), an amplifier of the TLR and NLR pathway, was decreased in ApoE(-/-) mice macrophages, leading to decreased recruitment of NF-κB onto the promoters of the TNF-α and IL-6. Our data suggest that in ApoE(-/-) mice hyperlipidemia disrupts the expression of PRRs, and cripples the host's capability to generate sufficient innate immune response to P. gingivalis, which may facilitate immune evasion, subgingival colonization and establishment of P. gingivalis in the periodontal niche.
authors: School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
authors: Lang
authors: L
authors: Lei
authors: Houxuan
authors: H
authors: Li
authors: Fuhua
authors: F
authors: Yan
authors: Yin
authors: Y
authors: Xiao
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D016866:Bacteroidaceae Infections / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006949:Hyperlipidemias / Q000150:complications / Q000276:immunology*; D007113:Immunity, Innate; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010510:Periodontal Diseases / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D059467:Transcriptome
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D051192:Receptors, Pattern Recognition; C498144:Rela protein, mouse; D051996:Transcription Factor RelA
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