AUTHOR=Tong Yue , Xin Yue , Fu Lanqing , Shi Jia , Sun Ying 

TITLE=Excessive neutrophil extracellular trap formation induced by Porphyromonas gingivalis lipopolysaccharide exacerbates inflammatory responses in high glucose microenvironment

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1108228

DOI=10.3389/fcimb.2023.1108228

ISSN=2235-2988

ABSTRACT=Neutrophil extracellular trap (NET) is a novel defense strategy of neutrophils and found to be induced by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) or high glucose. The aim of this study was to investigate the roles and mechanisms of NET formation in high glucose inflammatory microenvironment. NETs were induced by 1 μg/ml P. gingivalis LPS and/or 25 mM glucose. P. gingivalis LPS enhanced the formation of NETs and increased the levels of extracellular DNA in high glucose microenvironment (p < 0.05). Compared with normal glucose inflammatory microenvironment, quantities of extra- and intracellular viable P. gingivalis in neutrophils exposed to NETs induced in high glucose inflammatory one were increased (p < 0.05) and the expressions of NLRP3 and IL-1β were dramatically increased in macrophages co-cultured with NETs from high glucose inflammatory microenvironment (p < 0.05). In addition, levels of ROS, intracellular Ca2+, p-PKC βII, p-MEK, p-ERK, ORAI1 and ORAI2 were increased in neutrophils stimulated with both high glucose and P. gingivalis LPS compared with the single stimulus groups (p < 0.05). Taken together, in high glucose inflammatory microenvironment, formation of NETs was enhanced via oxidative stress, which failed to reverse the decreased bactericidal capacity in high glucose microenvironment, and instead aggravated the subsequent inflammatory responses.