SOCS-1 participates in negative regulation of LPS responses.
SOCS-1 is a negative regulatory molecule of the JAK-STAT signal cascade. Here, we demonstrate that SOCS-1 is a critical downregulating factor for LPS signal pathways. SOCS-1 expression was promptly induced in macrophages upon LPS stimulation. SOCS-1-deficient mice were highly sensitive to LPS-induced shock and produced increased levels of inflammatory cytokines. Introduction of SOCS-1 inhibited LPS-induced NF-kappaB and STAT1 activation in macrophages. Furthermore, LPS tolerance, a refractory state to second LPS stimulation, was not observed in SOCS-1-deficient mice. These results suggest SOCS-1 as an essential, negative regulator in LPS responses that protects the host from harmful overresponses to LPS and may provide new insight into the endotoxin-induced fatal syndrome that occasionally occurs following infection.
Nakagawa
Reiko
R
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Japan. naka@imed3.med.osaka-u.ac.jp
Naka
Tetsuji
T
Tsutsui
Hiroko
H
Fujimoto
Minoru
M
Kimura
Akihiro
A
Abe
Tatsuo
T
Seki
Ekihiro
E
Sato
Shintaro
S
Takeuchi
Osamu
O
Takeda
Kiyoshi
K
Akira
Shizuo
S
Yamanishi
Koichi
K
Kawase
Ichirou
I
Nakanishi
Kenji
K
Kishimoto
Tadamitsu
T
D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D012772:Shock, Septic / Q000276:immunology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000276:immunology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; C491590:Socs1 protein, mouse; C494080:Stat1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators