Effects of Endotoxin Tolerance Induced by Porphyromonas gingivalis Lipopolysaccharide on Inflammatory Responses in Neutr
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ORIGINAL ARTICLE
Effects of Endotoxin Tolerance Induced by Porphyromonas gingivalis Lipopolysaccharide on Inflammatory Responses in Neutrophils Jian-yu Gu,1,2 Yu-jie Liu,1,2 Xiang-qing Zhu,1,2,3 Jia-ying Qiu,1,2,4 and Ying Sun
1,2,5
Periodontitis is a dental plaque–induced chronic inflammatory disease. Longterm exposure of the host to periodontal pathogens leads to a hyporesponsive state to the following stimulations, which is described as endotoxin tolerance. Neutrophils are the most abundant innate immune cells in the body. To clarify the roles of endotoxin tolerance in periodontitis, inflammatory responses in Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS)–tolerized neutrophils were explored in this study. Here, apoptosis and respiratory burst in neutrophils upon single or repeated P. gingivalis LPS stimulations were explored by flow cytometry. Cytokine production (TNF-α, IL-8, and IL-10) in tolerized neutrophils or neutrophils co-cultured with peripheral blood mononuclear cells was determined by ELISA. Phagocytosis of P. gingivalis by tolerized neutrophils was also assayed by flow cytometry. In addition, quality and quantitation of neutrophil extracellular trap (NET) formation were detected using immunofluorescence microscope and microplate reader, respectively. The protein expressions of extracellular signal–regulated kinase1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) were examined to identify possible mechanisms for the abovementioned changes. Tolerance induced by P. gingivalis LPS significantly suppressed apoptosis, reactive oxygen species (ROS) generation, and phagocytosis in neutrophils (p < 0.05). In both neutrophils alone and co-culture system, repeated P. gingivalis LPS stimulations significantly decreased TNF-α production, but increased IL-10 secretion (p < 0.05). Moreover, in tolerized neutrophils, NET formations were strengthened and there were more released extracellular DNA (p < 0.05). In
Abstract—
Jian-yu Gu and Yu-jie Liu contributed equally to this work. 1
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China 2 Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China 3 Department of Stomatology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China 4 Department of Periodontology, Suzhou Stomatology Hospital, Suzhou, China 5 To whom correspondence should be addressed at Department of Periodontology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China. E-mail: [email protected]
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Gu, Liu, Zhu, Qiu, and Sun P. gingivalis LPS-tolerized neutrophils, phosphorylation of ERK1/2 was suppressed compared with that in non-tolerized cells. Taken together, immune responses in neutrophils were reprogrammed by P. gingivalis LPS-induced tolerance, which might be related with the development of inflammation in periodontal
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