title: Elevated MicroRNA-128 in Periodontitis Mitigates Tumor Necrosis Factor-α Response via p38 Signaling Pathway in Macrophages.
abstract: Periodontitis is a chronic inflammatory disease resulting from an inflammatory response to subgingival plaque bacteria, including Porphyromonas gingivalis. MicroRNA (miRNA) is a current focus in regulating the inflammatory processes. In this study, the inflammatory miRNA expression in gingival tissues of patients with periodontitis and of healthy individuals is compared, and its role in regulating the inflammatory response is examined.
  
  
  
  Gingival tissues from patients with periodontitis and healthy individuals were collected for miRNA microarray. THP-1 and CA9-22 cells were challenged with P. gingivalis, and miRNA expression was determined by real-time polymerase chain reaction. Target genes for miRNA were predicted using TargetScanHuman database, and miRNA gene expressions were reviewed using public databases. For the functional study, THP-1 cells were transfected with a miRNA-128 mimic, and target gene expression was compared with THP-1 cells challenged with P. gingivalis. For the tolerance test, THP-1 cells transfected with miRNA-128 mimic were treated with phorbol 12-myristate 13-acetate (PMA) or paraformaldehyde (PFA)-fixed Escherichia coli. Tumor necrosis factor (TNF)-α production was determined by enzyme-linked immunosorbent assay, and mitogen-activated protein kinase (MAPK) protein phosphorylation was determined by Western blot.
  
  
  
  Gingival tissues from patients with periodontitis showed increased expression of miRNA-128, miRNA-34a, and miRNA-381 and decreased expression of miRNA-15b, miRNA-211, miRNA-372, and miRNA-656. THP-1 cells and CA9-22 cells challenged with P. gingivalis showed increased miRNA-128 expression. Among the predicted miRNA-128 target genes, several genes that are involved in MAPK signaling pathway showed similar gene expression pattern between P. gingivalis challenge and miRNA-128 mimic transfection. In THP-1 cells transfected with miRNA-128 mimic, TNF-α production was lower, and phosphorylation of p38 was inhibited when challenged with PMA or PFA-fixed E. coli.
  
  
  
  miRNA-128 may be involved in mitigating the inflammatory response induced by P. gingivalis in periodontitis.
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Hee Sam
authors.initials: HS
authors.lastname: Na
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Song
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Pusan National University.
authors.forename: Hyung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Periodontics, School of Dentistry, Pusan National University.
authors.forename: Ju Youn
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Periodontics, School of Dentistry, Pusan National University.
authors.forename: Jeom-Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Chung
mesh_terms: D004926:Escherichia coli; D006801:Humans; D008264:Macrophages; D035683:MicroRNAs; D010518:Periodontitis / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Immune tolerance; TNF-α; microRNAs; periodontitis