TY - JOUR
T1 - SOCS-1 participates in negative regulation of LPS responses
AU - Nakagawa, Reiko
AU - Naka, Tetsuji
AU - Tsutsui, Hiroko
AU - Fujimoto, Minoru
AU - Kimura, Akihiro
AU - Abe, Tatsuo
AU - Seki, Ekihiro
AU - Sato, Shintaro
AU - Takeuchi, Osamu
AU - Takeda, Kiyoshi
AU - Akira, Shizuo
AU - Yamanishi, Koichi
AU - Kawase, Ichirou
AU - Nakanishi, Kenji
AU - Kishimoto, Tadamitsu
N1 - Funding Information:
We gratefully acknowledge the provision of STAT1 KO mice by Dr. R.D. Schreiber at Washington University, anti-murine MD2 mAb by Dr. K. Miyake (Tokyo University, Tokyo, Japan), pCGN-HA-IRAK1-N cDNA by Dr. Z. Cao (Tularik, CA), and IRAK cDNA by Dr. J. Inoue (Keio University, Tokyo, Japan). We thank Dr. S. Nagata (Osaka University) and Dr. K. Matsumoto (Nagaya University, Aichi, Japan) for helpful discussions, Mr. M. Tanei (KAC Corp, Shiga, Japan) for expert management of the mice, and Ms. A. Saito and Ms. R. Shimbo for their secretarial assistance. This work was supported in part by grants, a grant-in-aid, and a Hitec Research Center grant from the Ministry of Education, Science, and Culture, Japan.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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-κB 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.
AB - 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-κB 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.
UR - http://www.scopus.com/inward/record.url?scp=18744371050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18744371050&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(02)00449-1
DO - 10.1016/S1074-7613(02)00449-1
M3 - Article
C2 - 12433373
AN - SCOPUS:18744371050
SN - 1074-7613
VL - 17
SP - 677
EP - 687
JO - Immunity
JF - Immunity
IS - 5
ER -
