Porphyromonas gingivalis lipopolysaccharide regulates interleukin (IL)-17 and IL-23 expression via SIRT1 modulation in human periodontal ligament cells.
Increased interleukin (IL)-17 and IL-23 levels exist in the gingival tissue of periodontitis patients, but the precise molecular mechanisms that regulate IL-17 and IL-23 production remain unknown. The aim of this study was to explore the role of SIRT1 signaling on Porphyromonas gingivalis lipopolysaccharide (LPS)-induced IL-17 and IL-23 production in human periodontal ligament cells (hPDLCs). IL-17 and IL-23 production was significantly increased in LPS-treated cells. LPS treatment also led to the upregulation of SIRT1 mRNA and protein expression. LPS-induced IL-17 and IL-23 upregulation was attenuated by pretreatment with inhibitors of phosphoinositide 3-kinase (PI3K), p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and NF-κB, as well as neutralizing antibodies against Toll-like receptors (TLRs) 2 and 4. Sirtinol treatment (a known SIRT1 inhibitor) or SIRT1 knockdown by small interfering RNA blocked LPS-stimulated IL-17 and IL-23 expression. Further investigation showed that LPS decreased osteoblast markers (i.e., ALP, OPN, and BSP) and concomitantly increased osteoclast markers (i.e., RANKL and M-CSF). This response was attenuated by inhibitors of the PI3K, p38, ERK, JNK, NF-κB, and SIRT1 pathways. These findings, for the first time, suggest that human periodontopathogen P. gingivalis LPS is implicated in periodontal disease bone destruction and may mediate IL-17 and IL-23 release from hPDLCs. This process is dependent, at least in part, on SIRT1-Akt/PI3K-MAPK-NF-κB signaling.
Department of Preventive and Social Dentistry, School of Dentistry, Institute of Oral Biology, Kyung Hee University, Seoul, Republic of Korea.
Yong-Duk
YD
Park
Young-Suk
YS
Kim
Yu-Mi
YM
Jung
Sang-Im
SI
Lee
Young-Man
YM
Lee
Jae-Beum
JB
Bang
Eun-Cheol
EC
Kim
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016966:Porphyromonas gingivalis / Q000737:chemistry; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism
D000469:Alkaline Phosphatase; D057134:Antibodies, Neutralizing; D001549:Benzamides; D004791:Enzyme Inhibitors; D020381:Interleukin-17; D053759:Interleukin-23; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D009284:Naphthols; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D053245:RANK Ligand; D056564:Sirtuin 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C505688:TNFSF11 protein, human; C439060:sirtinol; C447939:SIRT1 protein, human