c-Fos suppresses systemic inflammatory response to endotoxin

Neelanjan Ray; Masayoshi Kuwahara; Yasunari Takada; Kenta Maruyama; Tomohiro Kawaguchi; Hirokazu Tsubone; Hiromichi Ishikawa; Koichi Matsuo

doi:10.1093/intimm/dxl004

c-Fos suppresses systemic inflammatory response to endotoxin

Neelanjan Ray, Masayoshi Kuwahara, Yasunari Takada, Kenta Maruyama, Tomohiro Kawaguchi, Hirokazu Tsubone, Hiromichi Ishikawa, Koichi Matsuo

Collaborative Research Resources (Laboratory of Cell and Tissue Biology)

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

58 Citations (Scopus)

Abstract

We explored the role of the transcription factor c-Fos in lipopolysaccharide (LPS)-induced cytokine response using mice lacking c-Fos (Fos^-/- mice). Compared with wild-type controls, Fos^-/- macrophages and mice showed significantly enhanced production of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12 p40, but reduced production of the anti-inflammatory cytokine IL-10. Bandshift analysis revealed that LPS-induced NF-κB binding activity to a functional site in the TNF-α promoter was significantly higher in Fos -/- than in wild-type macrophages. Using telemetry, we monitored body temperature and heart rate after LPS injection and found that Fos^-/- mice undergo more severe hypothermia and bradycardia than wild-type mice. Such shock responses in Fos^-/- mice were significantly reversed by neutralizing TNF-α. These data reveal a novel in vivo role for c-Fos as an anti-inflammatory transcription factor acting through suppression of NF-κB activity.

Original language	English
Pages (from-to)	671-677
Number of pages	7
Journal	International immunology
Volume	18
Issue number	5
DOIs	https://doi.org/10.1093/intimm/dxl004
Publication status	Published - 2006 May 15

Keywords

AP-1
Body temperature
Cytokines
Knockout mice
NF-κB
TNF-α
Telemetry

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1093/intimm/dxl004

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title = "c-Fos suppresses systemic inflammatory response to endotoxin",

abstract = "We explored the role of the transcription factor c-Fos in lipopolysaccharide (LPS)-induced cytokine response using mice lacking c-Fos (Fos-/- mice). Compared with wild-type controls, Fos-/- macrophages and mice showed significantly enhanced production of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12 p40, but reduced production of the anti-inflammatory cytokine IL-10. Bandshift analysis revealed that LPS-induced NF-κB binding activity to a functional site in the TNF-α promoter was significantly higher in Fos -/- than in wild-type macrophages. Using telemetry, we monitored body temperature and heart rate after LPS injection and found that Fos-/- mice undergo more severe hypothermia and bradycardia than wild-type mice. Such shock responses in Fos-/- mice were significantly reversed by neutralizing TNF-α. These data reveal a novel in vivo role for c-Fos as an anti-inflammatory transcription factor acting through suppression of NF-κB activity.",

keywords = "AP-1, Body temperature, Cytokines, Knockout mice, NF-κB, TNF-α, Telemetry",

author = "Neelanjan Ray and Masayoshi Kuwahara and Yasunari Takada and Kenta Maruyama and Tomohiro Kawaguchi and Hirokazu Tsubone and Hiromichi Ishikawa and Koichi Matsuo",

note = "Funding Information: We thank Kiyoshi Takeda for discussion, and Luc Van Kaer, Erwin F. Wagner and Shigeo Koyasu for critical reading of the manuscript. This work was funded in part by a Keio University Special Grant-in-Aid for Innovative Collaborative Research Projects, a grant-in-aid from the 21st Century COE program at Keio University from the Ministry of Education, Culture, Sports, Science and Technology, the Waksman Foundation, the National Science Foundation East Asia Summer Institutes Program and the Medical Scholars Program at Vanderbilt University School of Medicine.",

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doi = "10.1093/intimm/dxl004",

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T1 - c-Fos suppresses systemic inflammatory response to endotoxin

AU - Ray, Neelanjan

AU - Kuwahara, Masayoshi

AU - Takada, Yasunari

AU - Maruyama, Kenta

AU - Kawaguchi, Tomohiro

AU - Tsubone, Hirokazu

AU - Ishikawa, Hiromichi

AU - Matsuo, Koichi

N1 - Funding Information: We thank Kiyoshi Takeda for discussion, and Luc Van Kaer, Erwin F. Wagner and Shigeo Koyasu for critical reading of the manuscript. This work was funded in part by a Keio University Special Grant-in-Aid for Innovative Collaborative Research Projects, a grant-in-aid from the 21st Century COE program at Keio University from the Ministry of Education, Culture, Sports, Science and Technology, the Waksman Foundation, the National Science Foundation East Asia Summer Institutes Program and the Medical Scholars Program at Vanderbilt University School of Medicine.

PY - 2006/5/15

Y1 - 2006/5/15

N2 - We explored the role of the transcription factor c-Fos in lipopolysaccharide (LPS)-induced cytokine response using mice lacking c-Fos (Fos-/- mice). Compared with wild-type controls, Fos-/- macrophages and mice showed significantly enhanced production of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12 p40, but reduced production of the anti-inflammatory cytokine IL-10. Bandshift analysis revealed that LPS-induced NF-κB binding activity to a functional site in the TNF-α promoter was significantly higher in Fos -/- than in wild-type macrophages. Using telemetry, we monitored body temperature and heart rate after LPS injection and found that Fos-/- mice undergo more severe hypothermia and bradycardia than wild-type mice. Such shock responses in Fos-/- mice were significantly reversed by neutralizing TNF-α. These data reveal a novel in vivo role for c-Fos as an anti-inflammatory transcription factor acting through suppression of NF-κB activity.

AB - We explored the role of the transcription factor c-Fos in lipopolysaccharide (LPS)-induced cytokine response using mice lacking c-Fos (Fos-/- mice). Compared with wild-type controls, Fos-/- macrophages and mice showed significantly enhanced production of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12 p40, but reduced production of the anti-inflammatory cytokine IL-10. Bandshift analysis revealed that LPS-induced NF-κB binding activity to a functional site in the TNF-α promoter was significantly higher in Fos -/- than in wild-type macrophages. Using telemetry, we monitored body temperature and heart rate after LPS injection and found that Fos-/- mice undergo more severe hypothermia and bradycardia than wild-type mice. Such shock responses in Fos-/- mice were significantly reversed by neutralizing TNF-α. These data reveal a novel in vivo role for c-Fos as an anti-inflammatory transcription factor acting through suppression of NF-κB activity.

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KW - Cytokines

KW - Knockout mice

KW - NF-κB

KW - TNF-α

KW - Telemetry

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JO - International Immunology

JF - International Immunology

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c-Fos suppresses systemic inflammatory response to endotoxin

Abstract

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