acetaminophen modulates the transcriptional response to recombinant interferon-β对乙酰氨基酚调节转录响应interferon-β重组.pdfVIP

Acetaminophen Modulates the Transcriptional Response to Recombinant Interferon-b 1 1 1 1 2 Aaron Farnsworth *, Anathea S. Flaman , Shiv S. Prasad , Caroline Gravel , Andrew Williams , Carole L. Yauk2, Xuguang Li1 1 Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario, Canada, 2 Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada Abstract Background: Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration. Methodology/Principal Findings: We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-b treatment. CD-1 mice were administered acetaminophen (APAP), interferon-b (IFN-b) or a combination of IFN-b+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-b. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IkBK/NF-kB