[PDF][PDF] SOCS1/JAB is a negative regulator of LPS-induced macrophage activation
Immunity, 2002•cell.com
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 NO 2− synthesis and
TNFα production were augmented in SOCS1−/− macrophages. Furthermore, LPS tolerance …
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 NO 2− synthesis and
TNFα production were augmented in SOCS1−/− macrophages. Furthermore, LPS tolerance …
Abstract
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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