Double-stranded RNA activates a p38 MAPK-dependent cell survival program in biliary epithelia

Laura Tadlock, Yoko Yamagiwa, Carla Marienfeld, Tushar Patel

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Double-stranded RNA (dsRNA) is produced during replicative viral infection or genotoxic stress. Thus knowledge of the cellular response to dsRNA is necessary to understand the effects of DNA damage or viral infection in biliary epithelia. We assessed the effect of dsRNA on biliary epithelial cell proliferation and apoptosis and the role of the stress-activated p38 MAPK signaling pathway in these responses. dsRNA did not induce apoptosis or proliferation in Mz-ChA-1 human malignant cholangiocytes, but decreased cytotoxicity induced by camptothecin or tumor necrosis factor-related apoptosis inducing ligand and decreased activity of caspases 3, 8, and 9. Furthermore, dsRNA increased p38 MAPK and JNK kinase active site phosphorylation but had no effect on either MAPK kinase (MEK)1/2 or protein kinase R phosphorylation. Inhibition of p38 MAPK with SB-203580 increased basal caspase activity. Thus dsRNA stimulates a p38 MAPK-dependent cell-survival pathway in biliary epithelial cells that may modulate the response of the biliary epithelia to dsRNA produced during genotoxic injury or virus infection.

Original languageEnglish (US)
Pages (from-to)G924-G932
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume284
Issue number6 47-6
DOIs
StatePublished - Jun 1 2003

Keywords

  • Apoptosis
  • Caspase
  • Cholangiocyte
  • Mitogen-activated protein kinase
  • Protein kinase R

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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