IL-11 activates human endothelial cells to resist immune-mediated injury

J Immunol. 2000 Apr 1;164(7):3837-46. doi: 10.4049/jimmunol.164.7.3837.

Abstract

IL-11, a gp130-signaling cytokine, is protective in several in vivo models of immune-mediated and inflammatory injury. HUVECs express IL-11 receptor alpha-chain and gp130. Human IL-11 causes rapid (2-10 min) tyrosine phosphorylation of gp130. IL-11 at 0.1 and 10 ng/ml induces tyrosine phosphorylation of STAT3 and STAT1, respectively, although maximal responses require 50 ng/ml. Phospho-STAT3 and phospho-STAT1 levels peak rapidly (2.5 min) and disappear by 60 min. The p42 and p44 mitogen-activated protein kinases (MAPKs) are phosphorylated in response to 0.3 ng/ml IL-11 with maximal activation at 30 ng/ml IL-11. Phosphorylation of p42 and p44 MAPKs, which can be prevented by a mitogen-activated protein/extracellular signal-related kinase kinase-1 inhibitor, peaks by 15-20 min and largely disappears by 40 min. IL-11 does not activate NF-kappaB nor does it inhibit NF-kappaB activation by TNF. Similarly, IL-11 neither induces E-selectin or ICAM-1 nor blocks induction by TNF. Although IL-11 does not alter class I MHC complex molecule expression, pretreatment with 0.5 ng/ml IL-11 partially protects HUVECs against lysis by allospecific class I MHC-restricted cytolytic T lymphocytes or by anti-class I MHC Ab plus heterologous C. IL-11-induced cytoprotection is protein synthesis dependent and may depend on mitogen-activated protein/extracellular signal-related kinase kinase-1. Our results indicate that low (i.e., STAT3- and MAPK-activating) concentrations of IL-11 confer resistance to immune-mediated injury in cultured HUVECs without inhibiting proinflammatory responses.

MeSH terms

  • Antigens, CD / metabolism
  • Cells, Cultured
  • Complement System Proteins / immunology
  • Cytokine Receptor gp130
  • Cytotoxicity, Immunologic
  • DNA-Binding Proteins / metabolism
  • Dose-Response Relationship, Immunologic
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Enzyme Activation / immunology
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / immunology*
  • Inflammation Mediators / toxicity
  • Interleukin-11 / metabolism
  • Interleukin-11 / pharmacology
  • Interleukin-11 / physiology*
  • Interleukin-11 Receptor alpha Subunit
  • Membrane Glycoproteins / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / physiology
  • Phosphorylation
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin-11
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Signal Transduction / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Trans-Activators / metabolism
  • Tyrosine / metabolism
  • Umbilical Veins

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • IL11RA protein, human
  • IL6ST protein, human
  • Inflammation Mediators
  • Interleukin-11
  • Interleukin-11 Receptor alpha Subunit
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Interleukin
  • Receptors, Interleukin-11
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Cytokine Receptor gp130
  • Tyrosine
  • Complement System Proteins
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases