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Updated: Jun 13, 2026

Cholesterol Efflux Assay
Published on: March 6, 2012
IFN-lambda endocytosis and IFN-lambda responsive promoter activation are dependent on cholesterol
Okki Cho1, Seung Ho Hong, Jung Sik Kim
1Department of Microbiology, Ajou University School of Medicine, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
Insights
Interferon-lambdas (IFN-lambdas) are internalized by cells, a process crucial for their function. Inhibiting this endocytosis impacts antiviral gene activation, suggesting a role in immunity.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Receptor endocytosis influences signaling for many immunomodulatory molecules.
- The endocytosis of interferon-lambdas (IFN-lambdas) and its functional consequences remain largely uncharacterized.
Purpose of the Study:
- To investigate the mechanism of IFN-lambda internalization.
- To determine the impact of IFN-lambda endocytosis on its biological function and downstream signaling.
Main Methods:
- Utilized HepG2 cells to study IFN-lambda uptake.
- Employed cholesterol depletion and genetic inhibition to block endocytosis pathways.
- Assessed the activation of IFN-lambda responsive promoters.
Main Results:
- IFN-lambda internalization occurs via a cholesterol-dependent, dynamin-independent, and Rho GTPase-independent pathway.
- Inhibition of IFN-lambda endocytosis through cholesterol depletion significantly suppressed the activation of IFN-lambda responsive promoters.
- These findings highlight a novel mechanism regulating IFN-lambda signaling.
Conclusions:
- IFN-lambda endocytosis is an active process involved in regulating its function.
- This endocytic pathway plays a role in antiviral gene induction, impacting innate antiviral immunity.
Abstract:
Recently, a relationship between receptor endocytosis and downstream signaling has been documented for several immunomodulatory molecules. However, endocytosis of interferon-lambdas (IFN-lambdas) and its impact on IFN-lambda function has not been studied. We show that IFN-lambda is internalized through a cholesterol-dependent, dynamin-independent, and Rho family of GTPase-independent pathway in HepG2 cells. Furthermore, we demonstrate that inhibition of IFN-lambda endocytosis by cholesterol depletion suppresses the activation of IFN-lambda responsive promoters. These results suggest that IFN-lambda endocytosis participates in regulating antiviral gene induction and thus may affect antiviral immunity.
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