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. We have shown that TNF‐α induced down‐regulation of functions of odontoblast‐like cells via the NF‐κB signaling pathway. However, TNF‐α‐exposed cells overexpressing macromolecular translocation inhibitor II (MTI‐II) or treated with a chemically synthesized MTI‐II peptide anti‐inflammatory drug (MPAID) regained their functions.