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Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells

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Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells. / Pauls, Eduardo; Shpiro, Natalia; Peggie, Mark; Young, Erick R.; Sorcek, Ronald J.; Tan, Li; Choi, Hwan Geun; Cohen, Philip.

In: Journal of Biological Chemistry, Vol. 287, No. 23, 01.06.2012, p. 19216-19228.

Research output: Contribution to journalArticle

Harvard

Pauls, E, Shpiro, N, Peggie, M, Young, ER, Sorcek, RJ, Tan, L, Choi, HG & Cohen, P 2012, 'Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells' Journal of Biological Chemistry, vol 287, no. 23, pp. 19216-19228., 10.1074/jbc.M112.345405

APA

Pauls, E., Shpiro, N., Peggie, M., Young, E. R., Sorcek, R. J., Tan, L., ... Cohen, P. (2012). Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells. Journal of Biological Chemistry, 287(23), 19216-19228. 10.1074/jbc.M112.345405

Vancouver

Pauls E, Shpiro N, Peggie M, Young ER, Sorcek RJ, Tan L et al. Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells. Journal of Biological Chemistry. 2012 Jun 1;287(23):19216-19228. Available from: 10.1074/jbc.M112.345405

Author

Pauls, Eduardo; Shpiro, Natalia; Peggie, Mark; Young, Erick R.; Sorcek, Ronald J.; Tan, Li; Choi, Hwan Geun; Cohen, Philip / Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells.

In: Journal of Biological Chemistry, Vol. 287, No. 23, 01.06.2012, p. 19216-19228.

Research output: Contribution to journalArticle

Bibtex - Download

@article{0ec2c0a673cc44d8873e61b77bbbcdf9,
title = "Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells",
author = "Eduardo Pauls and Natalia Shpiro and Mark Peggie and Young, {Erick R.} and Sorcek, {Ronald J.} and Li Tan and Choi, {Hwan Geun} and Philip Cohen",
year = "2012",
doi = "10.1074/jbc.M112.345405",
volume = "287",
number = "23",
pages = "19216--19228",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Essential Role for IKK beta in Production of Type 1 Interferons by Plasmacytoid Dendritic Cells

A1 - Pauls,Eduardo

A1 - Shpiro,Natalia

A1 - Peggie,Mark

A1 - Young,Erick R.

A1 - Sorcek,Ronald J.

A1 - Tan,Li

A1 - Choi,Hwan Geun

A1 - Cohen,Philip

AU - Pauls,Eduardo

AU - Shpiro,Natalia

AU - Peggie,Mark

AU - Young,Erick R.

AU - Sorcek,Ronald J.

AU - Tan,Li

AU - Choi,Hwan Geun

AU - Cohen,Philip

PY - 2012/6/1

Y1 - 2012/6/1

N2 - <p>Plasmacytoid dendritic cells (pDCs) are characterized by their ability to produce high levels of type 1 interferons in response to ligands that activate TLR7 and TLR9, but the signaling pathways required for IFN production are incompletely understood. Here we exploit the human pDC cell line Gen2.2 and improved pharmacological inhibitors of protein kinases to address this issue. We demonstrate that ligands that activate TLR7 and TLR9 require the TAK1-IKK beta signaling pathway to induce the production of IFN beta via a pathway that is independent of the degradation of I kappa B alpha. We also show that IKK beta activity, as well as the subsequent IFN beta-stimulated activation of the JAK-STAT1/2 signaling pathway, are essential for the production of IFN alpha by TLR9 ligands. We further show that TLR7 ligands CL097 and R848 fail to produce significant amounts of IFN alpha because the activation of IKK beta is not sustained for a sufficient length of time. The TLR7/9-stimulated production of type 1 IFNs is inhibited by much lower concentrations of IKK beta inhibitors than those needed to suppress the production of NF kappa B-dependent proinflammatory cytokines, such as IL-6, suggesting that drugs that inhibit IKK beta may have a potential for the treatment of forms of lupus that are driven by self-RNA and self-DNA-induced activation of TLR7 and TLR9, respectively.</p>

AB - <p>Plasmacytoid dendritic cells (pDCs) are characterized by their ability to produce high levels of type 1 interferons in response to ligands that activate TLR7 and TLR9, but the signaling pathways required for IFN production are incompletely understood. Here we exploit the human pDC cell line Gen2.2 and improved pharmacological inhibitors of protein kinases to address this issue. We demonstrate that ligands that activate TLR7 and TLR9 require the TAK1-IKK beta signaling pathway to induce the production of IFN beta via a pathway that is independent of the degradation of I kappa B alpha. We also show that IKK beta activity, as well as the subsequent IFN beta-stimulated activation of the JAK-STAT1/2 signaling pathway, are essential for the production of IFN alpha by TLR9 ligands. We further show that TLR7 ligands CL097 and R848 fail to produce significant amounts of IFN alpha because the activation of IKK beta is not sustained for a sufficient length of time. The TLR7/9-stimulated production of type 1 IFNs is inhibited by much lower concentrations of IKK beta inhibitors than those needed to suppress the production of NF kappa B-dependent proinflammatory cytokines, such as IL-6, suggesting that drugs that inhibit IKK beta may have a potential for the treatment of forms of lupus that are driven by self-RNA and self-DNA-induced activation of TLR7 and TLR9, respectively.</p>

U2 - 10.1074/jbc.M112.345405

DO - 10.1074/jbc.M112.345405

M1 - Article

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 23

VL - 287

SP - 19216

EP - 19228

ER -

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