Porphyromonas gingivalis -Derived Lipopolysaccharide Combines Hypoxia to Induce Caspase-1 Activation in Periodontitis

Periodontitis is defined as inflammation affecting the supporting tissue of teeth. Periodontal pathogens initiate the disease and induce inflammatory host response. Hypoxia may accelerate the process by producing pro-inflammatory factors. The aim of this study is to investigate the effect of ( ) lipopolysaccharides (LPS) and ( ) LPS in inducing caspase-1 activation in normoxic or hypoxic phases. The results showed that healthy gingiva was in a normoxic phase (HIF-1α negative). However, hypoxia appeared in periodontitis, in which NLRP3, cleaved-caspase-1, interleukin 1 beta (IL-1β) and caspase-1-induced cell death was enhanced in periodontitis specimens. The experiment showed that LPS slightly decreased the level of NLRP3 and IL-1β in gingival fibroblasts under normoxia. Surprisingly, hypoxia reversed the effects of LPS, highly promoted caspase-1 activation and IL-1β maturation. LPS, a kind of pathogen-associated molecular pattern (PAMP) was chosen to simulate the effect of Gram-negative microbiota. Different from LPS, LPS enhanced IL-1β maturation both in normoxia and hypoxia. Moreover, LPS turned normoxia into hypoxia phase in experimental periodontitis model, which may subsequently propel the inflammatory effect of LPS. It was concluded that LPS induced a hypoxic phase, which is a combing pathological factor of LPS in caspase-1 activating and IL-1β maturation in periodontal inflammation.