Related Experiment Video
Updated: May 14, 2026
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
MCPIP1 negatively regulates toll-like receptor 4 signaling and protects mice from LPS-induced septic shock
Shengping Huang1, Ruidong Miao, Zhou Zhou
1Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
Abstract:
Septic shock is one of leading causes of morbidity and mortality in hospital patients. However, genetic factors predisposing to septic shock are not fully understood. Our previous work showed that MCP-induced protein 1 (MCPIP1) was induced by lipopolysaccharides (LPSs), which then negatively regulates LPS-induced inflammatory signaling in vitro. Here we report that although MCPIP1 was induced by various toll-like receptor (TLR) ligands in macrophages, MCPIP1-deficient mice are extremely susceptible to TLR4 ligand (LPS)-induced septic shock and death, but not to the TLR2, 3, 5 and 9 ligands-induced septic shock. Consistently, LPS induced tumor necrosis factor α (TNFα) production in MCPIP1-deficient mice was 20-fold greater than that in their wild-type littermates. Further analysis revealed that MCPIP1-deficient mice developed severe acute lung injury after LPS injection and JNK signaling was highly activated in MCPIP1-deficient lungs after LPS stimulation. Finally, macrophage-specific MCPIP1 transgenic mice were partially protected from LPS-induced septic shock, suggesting that inflammatory cytokines from sources other than macrophages may significantly contribute to the pathogenesis of LPS-induced septic shock. Taken together, these results suggest that MCPIP1 selectively suppresses TLR4 signaling pathway and protects mice from LPS-induced septic shock.
Insights
MCPIP1 deficiency increases susceptibility to septic shock by dysregulating toll-like receptor 4 (TLR4) signaling. This protein selectively suppresses TLR4 pathways, protecting against lipopolysaccharide-induced inflammatory responses and acute lung injury.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Septic shock is a major cause of hospital mortality, with underlying genetic factors remaining unclear.
- MCPIP1 (MCP-induced protein 1) negatively regulates inflammatory signaling in vitro.
- Understanding genetic predispositions to septic shock is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of MCPIP1 in susceptibility to septic shock.
- To determine if MCPIP1 selectively regulates toll-like receptor (TLR) signaling pathways.
- To elucidate the protective mechanisms of MCPIP1 against lipopolysaccharide (LPS)-induced septic shock.
Main Methods:
- Utilized MCPIP1-deficient and macrophage-specific MCPIP1 transgenic mice.
- Administered various toll-like receptor (TLR) ligands, including lipopolysaccharide (LPS).
- Assessed susceptibility to septic shock, inflammatory cytokine production (TNFα), acute lung injury, and JNK signaling pathway activation.
Main Results:
- MCPIP1-deficient mice showed extreme susceptibility to LPS (TLR4 ligand)-induced septic shock and death, but not other TLR ligands.
- LPS induced significantly higher TNFα production and severe acute lung injury in MCPIP1-deficient mice.
- JNK signaling was highly activated in MCPIP1-deficient lungs post-LPS stimulation; macrophage-specific MCPIP1 transgenic mice were partially protected.
Conclusions:
- MCPIP1 plays a critical, selective role in suppressing the TLR4 signaling pathway.
- MCPIP1 protects against LPS-induced septic shock and associated acute lung injury.
- Inflammatory cytokines from non-macrophage sources also contribute to septic shock pathogenesis.
