Dental pulp cell-derived powerful inducer of TNF-α comprises PKR containing stress granule rich microvesicles

Shigeki Suzuki, Takao Fukuda, Shintaro Nagayasu, Jun Nakanishi, Kazuma Yoshida, Shizu Hirata-Tsuchiya, Yuki Nakao, Tomomi Sano, Akiko Yamashita, Satoru Yamada, Kouji Ohta, Hideki Shiba, Fusanori Nishimura

研究成果: ジャーナルへの寄稿記事

抄録

It is well known that dental pulp tissue can evoke some of the most severe acute inflammation observed in the human body. We found that dental pulp cells secrete a factor that induces tumor necrosis factor-α production from macrophages, and designated this factor, dental pulp cell-derived powerful inducer of TNF-α (DPIT). DPIT was induced in dental pulp cells and transported to recipient cells via microvesicles. Treatment of dental pulp cells with a PKR inhibitor markedly suppressed DPIT activity, and weak interferon signals were constitutively activated inside the cells. In recipient macrophages, stimulation with DPIT-containing supernatants from pulp cells resulted in activation of both nuclear factor-κB and MAP kinases like JNK and p38. Proteomics analyses revealed that many stress granule-related proteins were present in supernatants from dental pulp cells as well as microvesicle marker proteins like GAPDH, β-actin, HSPA8, HSPB1, HSPE1, and HSPD1. Furthermore, giant molecule AHNAK and PKR were detected in microvesicles derived from dental pulp cells, and gene silencing of AHNAK in dental pulp cells led to reduced DPIT activity. Thus, it appeared that the core protein of DPIT was PKR, and that PKR was maintained in an active state in stress granule aggregates with AHNAK and transported via microvesicles. The activity of DPIT for TNF-α induction was far superior to that of gram-negative bacterial endotoxin. Therefore, we, report for the first time, that active PKR is transported via microvesicles as stress granule aggregates and induces powerful inflammatory signals in macrophages.

元の言語英語
記事番号3825
ジャーナルScientific reports
9
発行部数1
DOI
出版物ステータス出版済み - 12 1 2019

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Dental Pulp
Macrophages
Proteins
Gene Silencing
p38 Mitogen-Activated Protein Kinases
Human Body
Endotoxins
Proteomics
Interferons
Actins
Tumor Necrosis Factor-alpha
Inflammation

All Science Journal Classification (ASJC) codes

  • General

これを引用

Dental pulp cell-derived powerful inducer of TNF-α comprises PKR containing stress granule rich microvesicles. / Suzuki, Shigeki; Fukuda, Takao; Nagayasu, Shintaro; Nakanishi, Jun; Yoshida, Kazuma; Hirata-Tsuchiya, Shizu; Nakao, Yuki; Sano, Tomomi; Yamashita, Akiko; Yamada, Satoru; Ohta, Kouji; Shiba, Hideki; Nishimura, Fusanori.

:: Scientific reports, 巻 9, 番号 1, 3825, 01.12.2019.

研究成果: ジャーナルへの寄稿記事

Suzuki, Shigeki ; Fukuda, Takao ; Nagayasu, Shintaro ; Nakanishi, Jun ; Yoshida, Kazuma ; Hirata-Tsuchiya, Shizu ; Nakao, Yuki ; Sano, Tomomi ; Yamashita, Akiko ; Yamada, Satoru ; Ohta, Kouji ; Shiba, Hideki ; Nishimura, Fusanori. / Dental pulp cell-derived powerful inducer of TNF-α comprises PKR containing stress granule rich microvesicles. :: Scientific reports. 2019 ; 巻 9, 番号 1.
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AU - Yoshida, Kazuma

AU - Hirata-Tsuchiya, Shizu

AU - Nakao, Yuki

AU - Sano, Tomomi

AU - Yamashita, Akiko

AU - Yamada, Satoru

AU - Ohta, Kouji

AU - Shiba, Hideki

AU - Nishimura, Fusanori

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