MHC class II engagement in brain endothelial cells induces protein kinase A-dependent IL-6 secretion and phosphorylation of cAMP response element-binding protein

J Immunol. 1999 Oct 1;163(7):3636-41.

Abstract

Activated endothelial cells can directly participate in immune responses by interacting with immunocompetent cells via class II MHC proteins. We show here that, after induction of MHC class II molecule expression by IFN-gamma, rat brain endothelial cells responded to MHC class II ligands, anti-MHC class II Abs, or superantigens by expression of IL-6 transcript and IL-6 secretion. This response was not affected by protein kinase C depletion but was mimicked by the cAMP-elevating agent forskolin and completely blocked by H89, an inhibitor of cAMP-dependent protein kinase (PKA). Involvement of a cAMP/PKA signaling pathway in response to MHC class II ligands was further demonstrated by measure of a dose-dependent increase in cAMP level and phosphorylation of the transcription factor cAMP response element-binding protein (CREB). Our results indicate that MHC class II engagement in brain endothelial cells is directly coupled to IL-6 production via a cAMP/PKA-dependent intracellular pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Cell Line, Transformed
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism*
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / metabolism*
  • Histocompatibility Antigens Class II / physiology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Ligands
  • Phosphorylation
  • Protein Kinase C / physiology
  • RNA, Messenger / biosynthesis
  • Rats

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Histocompatibility Antigens Class II
  • Interleukin-6
  • Ligands
  • RNA, Messenger
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C