Activation of toll-like receptor-3 induces interferon-lambda expression in human neuronal cells

Neuroscience. 2009 Mar 17;159(2):629-37. doi: 10.1016/j.neuroscience.2008.12.036. Epub 2009 Jan 1.

Abstract

We examined the gene expression and regulation of type III human interferon (IFN), IFN-lambda, in human neuronal cells. Human neuronal cells expressed endogenous IFN-lambda1 but not IFN-lambda2/3. Upon the activation of Toll-like receptor (TLR)-3 expressed in the neuronal cells by polyriboinosinic polyribocytidylic acid (PolyI:C), both IFN-lambda1 and IFN-lambda2/3 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-lambda receptor complex, interleukin-28 receptor alpha subunit (IL-28Ralpha) and IL-10Rbeta, as evidenced by the observations that exogenous IFN-lambda 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-lambda in human neuronal cells, which may have an important role in the innate neuronal protection against viral infections in the CNS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • 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-1 / immunology
  • Humans
  • Interferon Inducers / pharmacology
  • Interferons / metabolism*
  • Interleukin-10 Receptor beta Subunit / genetics
  • Interleukin-10 Receptor beta Subunit / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Poly I-C / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Time Factors
  • Toll-Like Receptor 3 / metabolism*
  • Tretinoin / pharmacology

Substances

  • Antineoplastic Agents
  • Interferon Inducers
  • Interleukin-10 Receptor beta Subunit
  • RNA, Messenger
  • Receptors, Cytokine
  • Toll-Like Receptor 3
  • interleukin 28alpha receptor
  • Tretinoin
  • Interferons
  • Cytosine Deaminase
  • APOBEC3 protein, human
  • Cytidine Deaminase
  • Poly I-C