AUTHOR=Cheng Ran , Liu Wen , Zhang Rui , Feng Yuchao , Bhowmick Neil A. , Hu Tao 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2017.00474

DOI=10.3389/fcimb.2017.00474

ISSN=2235-2988

ABSTRACT=<p>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 <italic>Porphyromonas gingivalis</italic> (<italic>P. gingivalis</italic>) lipopolysaccharides (LPS) and <italic>Escherichia coli</italic> (<italic>E. coli</italic>) 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 <italic>in vitro</italic> experiment showed that <italic>P. gingivalis</italic> LPS slightly decreased the level of NLRP3 and IL-1β in gingival fibroblasts under normoxia. Surprisingly, hypoxia reversed the effects of <italic>P. gingivalis</italic> LPS, highly promoted caspase-1 activation and IL-1β maturation. <italic>E. coli</italic> LPS, a kind of pathogen-associated molecular pattern (PAMP) was chosen to simulate the effect of Gram-negative microbiota. Different from <italic>P. gingivalis</italic> LPS, <italic>E. coli</italic> LPS enhanced IL-1β maturation both in normoxia and hypoxia. Moreover, <italic>E. coli</italic> LPS turned normoxia into hypoxia phase in experimental periodontitis model, which may subsequently propel the inflammatory effect of <italic>P. gingivalis</italic> LPS. It was concluded that <italic>E. coli</italic> LPS induced a hypoxic phase, which is a combing pathological factor of <italic>P. gingivalis</italic> LPS in caspase-1 activating and IL-1β maturation in periodontal inflammation.</p>