PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation

Hiroshi Iwata; Claudia Goettsch; Amitabh Sharma; Piero Ricchiuto; Wilson Wen Bin Goh; Arda Halu; Iwao Yamada; Hideo Yoshida; Takuya Hara; Mei Wei; Noriyuki Inoue; Daiju Fukuda; Alexander Mojcher; Peter C. Mattson; Albert László Barabási; Mark Boothby; Elena Aikawa; Sasha A. Singh; Masanori Aikawa

doi:10.1038/ncomms12849

PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation

Hiroshi Iwata, Claudia Goettsch, Amitabh Sharma, Piero Ricchiuto, Wilson Wen Bin Goh, Arda Halu, Iwao Yamada, Hideo Yoshida, Takuya Hara, Mei Wei, Noriyuki Inoue, Daiju Fukuda, Alexander Mojcher, Peter C. Mattson, Albert László Barabási, Mark Boothby, Elena Aikawa, Sasha A. Singh, Masanori Aikawa

Research output: Contribution to journal › Article › peer-review

Abstract (may include machine translation)

Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9-PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.

Original language	English
Article number	12849
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12849
State	Published - 31 Oct 2016
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms12849License: CC BY

Cite this

Iwata, H., Goettsch, C., Sharma, A., Ricchiuto, P., Goh, W. W. B., Halu, A., Yamada, I., Yoshida, H., Hara, T., Wei, M., Inoue, N., Fukuda, D., Mojcher, A., Mattson, P. C., Barabási, A. L., Boothby, M., Aikawa, E., Singh, S. A., & Aikawa, M. (2016). PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation. Nature Communications, 7, Article 12849. https://doi.org/10.1038/ncomms12849

@article{7e74c666433d4afcab88fe6adf7198f1,

title = "PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation",

abstract = "Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9-PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.",

author = "Hiroshi Iwata and Claudia Goettsch and Amitabh Sharma and Piero Ricchiuto and Goh, {Wilson Wen Bin} and Arda Halu and Iwao Yamada and Hideo Yoshida and Takuya Hara and Mei Wei and Noriyuki Inoue and Daiju Fukuda and Alexander Mojcher and Mattson, {Peter C.} and Barab{\'a}si, {Albert L{\'a}szl{\'o}} and Mark Boothby and Elena Aikawa and Singh, {Sasha A.} and Masanori Aikawa",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2016.",

year = "2016",

month = oct,

day = "31",

doi = "10.1038/ncomms12849",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

}

Iwata, H, Goettsch, C, Sharma, A, Ricchiuto, P, Goh, WWB, Halu, A, Yamada, I, Yoshida, H, Hara, T, Wei, M, Inoue, N, Fukuda, D, Mojcher, A, Mattson, PC, Barabási, AL, Boothby, M, Aikawa, E, Singh, SA & Aikawa, M 2016, 'PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation', Nature Communications, vol. 7, 12849. https://doi.org/10.1038/ncomms12849

TY - JOUR

T1 - PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation

AU - Iwata, Hiroshi

AU - Goettsch, Claudia

AU - Sharma, Amitabh

AU - Ricchiuto, Piero

AU - Goh, Wilson Wen Bin

AU - Halu, Arda

AU - Yamada, Iwao

AU - Yoshida, Hideo

AU - Hara, Takuya

AU - Wei, Mei

AU - Inoue, Noriyuki

AU - Fukuda, Daiju

AU - Mojcher, Alexander

AU - Mattson, Peter C.

AU - Barabási, Albert László

AU - Boothby, Mark

AU - Aikawa, Elena

AU - Singh, Sasha A.

AU - Aikawa, Masanori

PY - 2016/10/31

Y1 - 2016/10/31

N2 - Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9-PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.

AB - Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9-PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.

UR - http://www.scopus.com/inward/record.url?scp=84993972016&partnerID=8YFLogxK

U2 - 10.1038/ncomms12849

DO - 10.1038/ncomms12849

M3 - Article

C2 - 27796300

AN - SCOPUS:84993972016

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 12849

ER -

PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation

Abstract (may include machine translation)

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this