IFN-lambda endocytosis and IFN-lambda responsive promoter activation are dependent on cholesterol.
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.
Cho
Okki
O
Department of Microbiology, Ajou University School of Medicine, Youngtongku Wonchondong San 5, Suwon 442-749, Republic of Korea.
Hong
Seung Ho
SH
Kim
Jung Sik
JS
Yoon
Joon-Kee
JK
Kim
Kyongmin
K
Chwae
Yong-Joon
YJ
Shin
Ho-Joon
HJ
Park
Sun
S
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
D004791:Enzyme Inhibitors; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D007372:Interferons; D002784:Cholesterol; D020741:rho GTP-Binding Proteins; D034281:Dynamins