Activation of Toll-like receptor-3 induces interferon-λ expression in human neuronal cells

• Published in: Neuroscience 2009-03, Vol.159 (2), p.629-637
• Main Authors: Zhou, L, Wang, X, Wang, Y.J, Zhou, Y, Hu, S, Ye, L, Hou, W, Li, H, Ho, W.Z
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; APOBEC Deaminases; Brain - cytology; Cells, Cultured; Cytidine Deaminase; Cytosine Deaminase - metabolism; Dose-Response Relationship, Drug; Fetus; Gene Expression - drug effects; Gene Expression - genetics; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; HIV; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; interferon; Interferon Inducers - pharmacology; Interferons - metabolism; Interleukin-10 Receptor beta Subunit - genetics; Interleukin-10 Receptor beta Subunit - metabolism; Neurology; neuron; Neurons - drug effects; Neurons - metabolism; NT2-N; Poly I-C - pharmacology; Receptors, Cytokine - genetics; Receptors, Cytokine - metabolism; RNA, Messenger - metabolism; Time Factors; Toll-like receptor; Toll-Like Receptor 3 - metabolism; Tretinoin - pharmacology; virus
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.12.036

Abstract We examined the gene expression and regulation of type III human interferon (IFN), IFN-λ, in human neuronal cells. Human neuronal cells expressed endogenous IFN-λ1 but not IFN-λ2/3. Upon the activation of Toll-like receptor (TLR)-3 expressed in the neuronal cells by polyriboinosinic polyribocytidylic acid (PolyI:C), both IFN-λ1 and IFN-λ2/3 expression was significantly induced. The activation of TLR-3 also exhibited antiviral activity against pseudotyped human immunodeficiency virus (HIV)-1 infection of the neuronal cells. Human neuronal cells also expressed functional IFN-λ receptor complex, interleukin-28 receptor α subunit (IL-28Rα) and IL-10Rβ, as evidenced by the observations that exogenous IFN-λ treatment inhibited pseudotyped HIV-1 infection of the neuronal cells and induced the expression of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)3G/3F, the newly identified anti-HIV-1 cellular factors. These data provide direct and compelling evidence that there is intracellular expression and regulation of IFN-λ in human neuronal cells, which may have an important role in the innate neuronal protection against viral infections in the CNS.