Inhibitory effect of recombinant intracellular interleukin 1 receptor antagonist on endothelial cell activation

Cytokine. 1992 Jan;4(1):44-7. doi: 10.1016/1043-4666(92)90035-p.

Abstract

This investigation was designed to elucidate whether an intracellular version of interleukin 1 receptor antagonist (icIL-1ra) interferes with the action of IL-1 at the level of vascular cells. Recombinant icIL-1ra inhibited the IL-1-induced production of IL-6, IL-8 and monocyte chemotactic protein by human endothelial cells (HEC). Moreover, icIL-1ra inhibited induction of adhesion molecules by IL-1. Endotoxin lipopolysaccharide (LPS), an IL-1 inducer, stimulated a spectrum of functions in EC similar to that activated by IL-1, but icIL-1ra did not interfere with the LPS activation of EC. This observation suggests that induction of extracellular IL-1 is not an important intermediate event in the response of EC to LPS. Unlike LPS-stimulated monocytes, EC exposed to different inducers did not express appreciable levels of IL-1ra mRNA transcripts as assessed by northern blot analysis. IL-1ra produced by mononuclear phagocytes, represents a negative regulator circuit of the action of IL-1 on EC and could be important in the control of vascular participation in inflammation and immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / biosynthesis
  • Cells, Cultured
  • Chemokine CCL2
  • Chemotactic Factors / biosynthesis
  • Depression, Chemical
  • Drug Synergism
  • Endothelium, Vascular / drug effects*
  • Endotoxins / pharmacology
  • Gene Expression Regulation / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Infant, Newborn
  • Intercellular Adhesion Molecule-1
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / pharmacology*
  • Interleukins / biosynthesis
  • RNA, Messenger / biosynthesis
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Interleukin-1
  • Recombinant Proteins / pharmacology
  • Sialoglycoproteins / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Umbilical Veins
  • Vascular Cell Adhesion Molecule-1

Substances

  • Cell Adhesion Molecules
  • Chemokine CCL2
  • Chemotactic Factors
  • Endotoxins
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukins
  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Granulocyte-Macrophage Colony-Stimulating Factor