Manipulation of necroptosis by Porphyromonas gingivalis in periodontitis development

Abstract

To eliminate invading pathogens and keep homeostasis, host employs multiple approaches such as the non-inflammation associated-apoptosis, inflammation associated-necroptosis and pyroptosis, etc. Necroptosis is known as a highly pro-inflammatory form of cell death due to the release of massive damage-associated molecular patterns (DAMPs). For the first time, we reported that Porphyromonas gingivalis induced cellular necroptosis through receptor-interacting protein 1 (RIP1)/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway in monocytes. Necroptosis in THP-1 cells was induced by MLKL phosphorylation in vitro. P. gingivalis treated-THP-1 cells exhibited lower cell death rate with pretreatment of inhibitors RIP1 and MLKL, accompanied with attenuated TNF-α and IL-6 expressions. Moreover, the necroptosis risk was also reduced via gene silencing by RIP3 or MLKL in the P. gingivalis treated-THP-1 cell lines. We further explored P. gingivalis-induced necroptosis in animal models in vivo. Firstly, C57BL/6 mice were injected with P. gingivalis in the subcutaneous chamber model. Animals pretreated with MLKL inhibitor exhibited significantly enhanced P. gingivalis clearance; in addition, levels of TNF-α and IL-6 were notably decreased by 60% via MLKL inhibition. Secondly, P. gingivalis-induced periodontitis was utilized to investigate necroptosis related-periodontopathogensis. Positive staining of phosphorylated MLKL in mice periodontitis biopsies was detected to a higher degree, while larger amount of alveolar bone loss was observed in MLKL (-) group comparing to those in the MLKL (+) group. These findings may suggest that P. gingivalis play essential roles in necroptosis process during periodontitis, and our research may shed light on the further work on the related periodontopathogenesis investigation.

Therapeutic effect of Lianbeijuqin (a Chinese herbal cocktail) on periodontitis in rat

“…Thus, the search for more effective agents for suppression of microbial invasion, control of inflammation and protection of periodontal tissue are the primary objectives of periodontitis treatment [4,17]. The results of the current research revealed that LBJQ, an age-old Chinese herbal medicine formula, could significantly inhibit the growth of common oral pathogenic bacteria such as P.…”

“…It results in significant damage to surrounding tissue structures, leading to loss of teeth [1,2]. Besides tooth loss, periodontitis is associated with other discomforts such as gomphiasis, swelling and aching of gum, fever and bromopnea [3,4]. Current treatment and periodontal tissue regeneration strategies for periodontitis involve scaling, root planning and regenerative surgeries [5,6].…”

Egg yolk immunoglobulin interactions with Porphyromonas gingivalis to impact periodontal inflammation and halitosis

“…Anti-130k haemagglutinin IgY significantly inhibited P. gingivalis -associated haemagglutinating activity (Hamajima et al 2007 ). P. gingivalis were able to evade immune surveillance and avoid clearance, which facilitates local invasions of periodontal tissues; while the host also generated immune responses to the bacterial challenge, which contributed to a bactericidal effect but may also lead to periodontal destruction (Ke et al 2016 ), which may develop into periodontitis and halitosis. Treatments of periodontitis and halitosis were based on mechanical debridement of infectious sites and pharmacological antibacterial therapy (Huang et al 2013 ).…”

“…About 700 different microbial species cause a number of different infections and inflammation in the oral cavity (Kuramitsu et al 2007 ; Tsuzukibashi et al 2014 ). The most common microbial oral diseases are periodontal inflammation (Ke et al 2016 ) and halitosis (Tanda et al 2015 ). These diseases may be caused by various anaerobic bacteria such as Streptococcus mutans , Porphyromonas gingivalis , Prevotella intermedia , and Fusobacterium nucleatum (Zhen et al 2008 ; Patra et al 2014 ).…”

Necroptosis in the periodontal homeostasis: Signals emanating from dying cells

“…Necroptosis, mediated by receptor-interacting protein kinase-3 (RIPK3) and its substrate mixed lineage kinase like (MLKL), is one recently characterized form of regulated necrosis, which plays an important role in infection-related diseases (Pasparakis & Vandenabeele, 2015). Recently, we found that it participates in the pathogenesis of periodontitis (Ke, Lei, Li, Li, & Yan, 2016). The periodontal homeostasis is maintained by a dynamic equilibrium between the cell death, proliferation, and differentiation.…”