Interferon α but not interleukin 12 activates STAT4 signaling in human vascular endothelial cells

Nicholas Torpey, Stephen E. Maher, Alfred L.M. Bothwell, Jordan S. Pober

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

STAT4 signaling, activated by either interleukin 12 (IL12) or interferon α (IFNα), promotes TH1 responses in CD4+ T cells. Vascular endothelial cells (EC) may also become polarized in response to various cytokines, favoring recruitment and activation of TH1 or TH2 effector cells. Here we have investigated the role of the STAT4 pathway in EC. Cultured human umbilical vein EC (HUVEC) express low levels of STAT4, which may be tyrosine-phosphorylated by treatment with IFNα but not IL12. This is because HUVEC lack both subunits of the IL12 receptor (IL12Rβ1 and IL12Rβ2), even following treatment with various cytokines. IL12 phosphorylation of STAT4 can be observed in HUVEC that have been transduced to express the IL12R. To identify STAT4-induced genes we pursued three approaches: analysis by DNA microarray and quantitative RT-PCR (Q-PCR) of the IL12 responses in IL12R-transduced EC; analysis by Q-PCR of IFNα responses in STAT4-overexpressing EC; and analysis of IFNα responses in U3A neuroblastoma cell lines that express either STAT1 or STAT4, but not both. In all three instances we observe STAT4-mediated induction of the chemokine monocyte chemoattractant protein 1 (MCP1) and suppressor of cytokine signaling 3 (SOCS3) mRNA, and we confirm the production of each protein in both IL12R-transduced EC and STAT4-transduced U3A cells. These observations reveal that there is a STAT4 response of EC, activated by IFNα but not IL12, and that it may modulate the proinflammatory behavior of EC.

Original languageEnglish (US)
Pages (from-to)26789-26796
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number25
DOIs
StatePublished - Jun 18 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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