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.

Macrophage proinflammatory response to the titanium alloy equipment in dental implantation

“…TGF-b1 is an important anti-inflammatory factor that can regulate immunosuppression and the inflammatory response (Lei et al, 2014;Yang et al, 2014). It plays a role in wound healing and local inflammatory reactions.…”

Gingival crevicular fluid oxidative stress level in patients with periodontal disease and hyperlipidemia

“…25,38,39,40 Our study found that patients with hyperlipidemia with periodontitis had higher GCF PC and MDA levels and lower GCF TAOC levels compared with systemically healthy subjects with periodontitis. Moreover, serum lipid levels varied according to periodontal status, but the difference was more pronounced among patients with hyperlipidemia than with normolipidemic subjects.…”

“…It has been claimed that the changes in lipid metabolism affect the host susceptibility via OS-related periodontal destruction. 25,38,39 In conclusion, increased OS and decreased TAOC level in the GCF of patients with hyperlipidemia and periodontal disease combination may be the possible cause of the alteration of host susceptibility to periodontal inflammation. Moreover, the bidirectional relationship between local periodontal and systemic factors should be taken into consideration in the treatment of patients with periodontal disease.…”

“…By interfering directly with membrane-bound receptors and altering gene expression, serum lipids play a role in tissue response, which when compromised, may predispose a patient to periodontal disease or exaggerated periodontal destruction. 38,39 This study's finding of higher OS markers and lower TAOC levels in patients with hyperlipidemia with periodontitis compared with patients with normolipidemia with periodontitis may be an indication of alterations in tissue response caused by lipid mediators at this later stage of periodontal destruction.…”

Relationship between periodontal disease and hyperlipidemia related to vascular events

“…Another factor that Lei et al, (2013) [57] attempt to on the study, is that the hyperlipidemia is related to obesity, and that it depends of the studied population and of the eating habits and life of the same. So, obesity is also a risk factor for coronary heart disease [58].…”