An in vitro experimental model of neuroinflammation: the induction of interleukin-6 in murine astrocytes infected with Theiler's murine encephalomyelitis virus, and its inhibition by oestrogenic receptor modulators

作者：Rubio Nazario^*; Cerciat Marie; Unkila Mikko; Garcia Segura Luis M; Arevalo Maria Angeles

来源：Immunology, 2011, 133(3): 360-369.

DOI：10.1111/j.1365-2567.2011.03448.x

• astrocytes
• encephalomyelitis virus
• inflammation
• interleukin-6
• oestrogen receptor modulators

P>This paper describes an experimental model of neuroinflammation based on the production of interleukin-6 (IL-6) by neural glial cells infected with Theiler's murine encephalomyelitis virus (TMEV). Production of IL-6 mRNA in mock-infected and TMEV-infected SJL/J murine astrocytes was examined using the Affymetrix murine genome U74v2 DNA microarray. The IL-6 mRNA from infected cells showed an eightfold increase in hybridization to a sequence encoding IL-6 located on chromosome number 5. Quantitative real-time reverse transcription PCR (qPCR) was used to study the regulation of IL-6 expression. The presence of IL-6 in the supernatants of TMEV-infected astrocyte cultures was quantified by ELISA and found to be weaker than in cultures of infected macrophages. The IL-6 was induced by whole TMEV virions, but not by Ad.beta Gal adenovirus, purified TMEV capsid proteins, or UV-inactivated virus. Two recombinant inflammatory cytokines, IL-1 alpha and tumour necrosis factor-alpha were also found to be potent inducers of IL-6. The secreted IL-6 was biologically active because it fully supported B9 hybridoma proliferation in a [3H]thymidine incorporation bioassay. The cerebrospinal fluid of infected mice contained IL-6 during the acute encephalitis phase, peaking at days 2-4 post-infection. Finally, this in vitro neuroinflammation model was fully inhibited, as demonstrated by ELISA and qPCR, by five selective oestrogen receptor modulators.

• 出版日期2011-7