IL-4-dependent CD86 expression requires JAK/STAT6 activation and is negatively regulated by PKCδ

Eric L. Deszo, Danett K. Brake, Keith W. Kelley, Gregory G. Freund

Research output: Contribution to journalArticlepeer-review

Abstract

CD86 expression is up-regulated in activated monocytes and macrophages by a mechanism that is not clearly defined. Here, we report that IL-4-dependent CD86 expression requires activation of ERK1/2 and JAK/STAT6 but is negatively regulated by PKCδ. PMA differentiated U937 monocytic cells when stimulated with IL-4 increased CD11b and CD86 expression by 52- and 98-fold, respectively. PMA+IL-4 treatment also induced a synergistic enhancement of ERK1/2 activation when compared to the effects of PMA and IL-4 alone. Use of the mitogen or extracellular kinase (MEK) inhibitor, PD98059, completely blocked up-regulation of CD11b and CD86 demonstrating the importance of MEK-activated ERK1/2. JAK inhibition with WHI-P154-abrogated IL-4-dependent CD11b and CD86 up-regulation and inhibited STAT6 tyrosine phosphorylation. Importantly, CD11b and CD86 expression were not reliant on IL-4-dependent activation of phosphatidylinositol 3′-kinase (PI 3-kinase). Blockade of PKCδ activation with rottlerin prevented CD11b expression but lead to a 75- and 213-fold increase in PMA and PMA+IL-4-dependent CD86 expression, respectively. As anticipated, increasing PKCδ activity with anti-sense reduction of CD45 increased CD11b expression and reduced CD86 expression. Likewise, rottlerin prevented nuclear localization of activated PKCδ. We conclude from these data that IL-4-dependent CD11b expression relies predominantly on enhanced activation of ERK1/2, while IL-4-dependent CD86 expression utilizes the JAK/STAT6 pathway.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalCellular Signalling
Volume16
Issue number2
DOIs
StatePublished - Feb 2004

Keywords

  • CD11b
  • CD86
  • MAP kinase
  • Monocytes/macrophages
  • PKC
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

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