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Published on: May 2, 2018
[Protection of PD-1 against LPS-induced endotoxemia and the underlying mechanism]
Li-Fen Yang1, Fang He, Jian Zhang
1Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.
Objective:
Gram-negative bacteria-induced multiple organ failure/dysfunction syndrome (MOF/MODS) is one of the leading causes of death through the world. The member of immunoglobulin family programmed death-1 (PD-1) is a negative immune regulator. This study investigated the protective effect of PD-1 as well as the underlying mechanism in LPS-induced endotoxemia.
Methods:
Ten PD-1(+/+) and ten PD-1 knockout (PD-1(-/-)) mice were injected peritoneally with LPS (10 mg/kg), and the survival was observed within 72 hrs after LPS injection. The other 40 PD-1(+/+) and 40 PD-1(-/-) mice were injected peritoneally with LPS (5 mg/kg). Blood samples were collected before injection and 1.5, 3 and 6 hrs after LPS injection (n=10 each time point). Serum levels of various inflammatory mediators were measured using ELISA.
Results:
The survival rate in PD-1(-/-) mice was noticeably lower than that in PD-1(+/+) mice after 10 mg/kg LPS injection. Serum levels of inflammatory mediators TNF-α, IL-1β, IL-12 and IL-17 in PD-1/mice were higher than those in PD-1(+/+) mice after 5 mg/kg LPS injection.
Conclusions:
PD-1 can protect mice from LPS-induced endotoxemia probably through its regulation on inflammatory mediator production.
Insights
Programmed death-1 (PD-1) protects against lipopolysaccharide (LPS)-induced endotoxemia by regulating inflammatory mediators. PD-1 knockout mice showed reduced survival and increased inflammatory markers, highlighting PD-1
Area of Science:
- Immunology
- Pathophysiology
- Molecular Biology
Context:
- Gram-negative bacteria sepsis leads to multiple organ dysfunction syndrome (MODS), a major global cause of mortality.
- Programmed death-1 (PD-1), an immunoglobulin family member, functions as a critical negative immune regulator.
- Lipopolysaccharide (LPS) is a potent endotoxin that triggers inflammatory responses and sepsis models.
Purpose:
- To investigate the protective role of PD-1 in a mouse model of LPS-induced endotoxemia.
- To elucidate the underlying mechanisms by which PD-1 influences the inflammatory response during endotoxemia.
Summary:
- Mice lacking PD-1 (PD-1(-/-)) exhibited significantly lower survival rates following LPS injection compared to wild-type (PD-1(+/+)) mice.
- Serum analysis revealed elevated levels of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-12, and IL-17, in PD-1(-/-) mice after LPS challenge.
- These findings suggest that PD-1 plays a crucial role in mitigating the severity of LPS-induced endotoxemia.
Impact:
- This research identifies PD-1 as a potential therapeutic target for managing sepsis and endotoxemia.
- Understanding PD-1's regulatory function in inflammation offers insights into host defense mechanisms against bacterial infections.
- The study provides a foundation for developing novel strategies to improve outcomes for patients suffering from sepsis-induced organ dysfunction.
