TY - JOUR
T1 - SOCS1/JAB is a negative regulator of LPS-induced macrophage activation
AU - Kinjyo, Ichiko
AU - Hanada, Toshikatsu
AU - Inagaki-Ohara, Kyoko
AU - Mori, Hiroyuki
AU - Aki, Daisuke
AU - Ohishi, Masanobu
AU - Yoshida, Hiroki
AU - Kubo, Masato
AU - Yoshimura, Akihiko
N1 - Funding Information:
We thank Y. Kawabata for technical assistance, Dr. T. Naka for critical discussion and comments, and M. Ohara for language assistance. This work was supported by Grants-in-Aid (for Y.A.) from the Ministry of Education, Science, Technology, Sports and Culture of Japan, the Japan Health Science Foundation, the Human Frontier Science Program, the Mochida Memorial Foundation, the Haraguchi Memorial Foundation, and the Japan Research Foundation for Clinical Pharmacology.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Bacterial lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor (TLR) 4. We show here that the suppressor of cytokine-signaling-1 (SOCS1/JAB) is rapidly induced by LPS and negatively regulates LPS signaling. SOCS1+/- mice or SOCS1-/- mice with interferon-γ (IFNγ)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO2- synthesis and TNFα production were augmented in SOCS1-/- macrophages. Furthermore, LPS tolerance, a protection mechanism against endotoxin shock, was also strikingly reduced in SOCS1-/- cells. LPS-induced I-κB and p38 phosphorylation was upregulated in SOCS1-/- macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-κB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.
AB - Bacterial lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor (TLR) 4. We show here that the suppressor of cytokine-signaling-1 (SOCS1/JAB) is rapidly induced by LPS and negatively regulates LPS signaling. SOCS1+/- mice or SOCS1-/- mice with interferon-γ (IFNγ)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO2- synthesis and TNFα production were augmented in SOCS1-/- macrophages. Furthermore, LPS tolerance, a protection mechanism against endotoxin shock, was also strikingly reduced in SOCS1-/- cells. LPS-induced I-κB and p38 phosphorylation was upregulated in SOCS1-/- macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-κB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.
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U2 - 10.1016/S1074-7613(02)00446-6
DO - 10.1016/S1074-7613(02)00446-6
M3 - Article
C2 - 12433365
AN - SCOPUS:0036850946
SN - 1074-7613
VL - 17
SP - 583
EP - 591
JO - Immunity
JF - Immunity
IS - 5
ER -
