title: The Novel NF-κB Inhibitor, MTI-II Peptide Anti-Inflammatory Drug, Suppresses Inflammatory Responses in Odontoblast-Like Cells.
abstract: Regulation of inflammation is important for pulp wound healing, including protective responses by odontoblast-like cells. However, methods for directly regulating pulp inflammation have not yet been described. The inflammatory response is mediated by a transcription factor, nuclear factor-κB (NF-κB), which activates inflammatory cytokines including tumor necrosis factor (TNF)-α. Macromolecular translocation inhibitor II (MTI-II) was previously demonstrated as an enhancer of the transcriptional activity of glucocorticoid-bound glucocorticoid receptor. Recently, a MTI-II peptide anti-inflammatory drug (MPAID) was bioengineered from the structure of MTI-II as an inhibitor of NF-κB transactivation. Here, we examined the effects of MTI-II and MPAID on the inflammatory responses of odontoblast-like cells. TNF-α inhibited alkaline phosphatase (ALP) activity, a marker of odontoblast/osteogenic differentiation, and induced NF-κB transcriptional activity in KN-3 cells, which are odontoblast-like cells derived from dental papilla cells of rat incisors, without affecting their viability. Exogenous expression of MTI-II suppressed the NF-κB transcriptional activity induced by TNF-α or overexpression of p65 (a main subunit of NF-κB) in the cells, whereas it failed to inhibit degradation of IκBα and nuclear translocation of p65 after TNF-α treatment, suggesting that MTI-II inhibits NF-κB transcriptional activity by modulating the duration of DNA binding by p65. MPAID also inhibited TNF-α-induced NF-κB transcriptional activity, the mRNA expression of IL-6 and IL-8, and IL-6 production. Furthermore, pretreatment of the cells with MPAID restored the inhibitory effect of TNF-α on ALP activity. These results suggest that MPAID may be able to regulate the inflammatory response and maintain a protective response of dental pulp. J. Cell. Biochem. 117: 2552-2558, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan.
authors.forename: Shizu
authors.initials: S
authors.lastname: Hirata-Tsuchiya
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Morotomi
authors.affiliation: Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan.
authors.forename: Eijiro
authors.initials: E
authors.lastname: Jimi
authors.affiliation: Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan. chi-aki-k@kyu-dent.ac.jp.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D013947:Thymosin; C044498:parathymosin alpha
keywords: MTI-II; MTI-II PEPTIDE ANTI-INFLAMMATORY DRUG; NF-κB; ODONTOBLAST-LIKE CELLS; TNF-α