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.
| Original language | English |
|---|---|
| Pages (from-to) | 2552-2558 |
| Number of pages | 7 |
| Journal | Journal of Cellular Biochemistry |
| DOIs | |
| Publication status | Published - Nov 1 2016 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
The Novel NF-κB Inhibitor, MTI-II Peptide Anti-Inflammatory Drug, Suppresses Inflammatory Responses in Odontoblast-Like Cells. / Nakayama, Kouhei; Hirata-Tsuchiya, Shizu; Okamoto, Kazuki; Morotomi, Takahiko; Jimi, Eijiro; Kitamura, Chiaki.
In: Journal of Cellular Biochemistry, 01.11.2016, p. 2552-2558.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Novel NF-κB Inhibitor, MTI-II Peptide Anti-Inflammatory Drug, Suppresses Inflammatory Responses in Odontoblast-Like Cells
AU - Nakayama, Kouhei
AU - Hirata-Tsuchiya, Shizu
AU - Okamoto, Kazuki
AU - Morotomi, Takahiko
AU - Jimi, Eijiro
AU - Kitamura, Chiaki
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
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U2 - 10.1002/jcb.25548
DO - 10.1002/jcb.25548
M3 - Article
C2 - 27012464
AN - SCOPUS:84986188739
SP - 2552
EP - 2558
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
ER -