title: IFN-lambda endocytosis and IFN-lambda responsive promoter activation are dependent on cholesterol.
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.
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
authors.forename: Okki
authors.initials: O
authors.lastname: Cho
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Hong
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Kim
authors.forename: Joon-Kee
authors.initials: JK
authors.lastname: Yoon
authors.forename: Kyongmin
authors.initials: K
authors.lastname: Kim
authors.forename: Yong-Joon
authors.initials: YJ
authors.lastname: Chwae
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Shin
authors.forename: Sun
authors.initials: S
authors.lastname: Park
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D007700:Kinetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D007372:Interferons; D002784:Cholesterol; D020741:rho GTP-Binding Proteins; D034281:Dynamins