Effects of oncostatin M on human cerebral endothelial cells and expression in inflammatory brain lesions

J Neuropathol Exp Neurol. 2001 Nov;60(11):1087-98. doi: 10.1093/jnen/60.11.1087.

Abstract

Oncostatin M (OSM) is a member of the interleukin (IL)-6 cytokine family and modulates inflammatory responses. Here we investigated the role of OSM as an immunoregulatory factor for human cerebral endothelial cells (HCEC). Using RT-PCR we detected transcripts of the receptor components involved in OSM signaling, gp130, OSM receptor (OSMR)-beta, and leukemia inhibitory factor receptor (LIFR), in HCEC. A parallel FACS analysis revealed surface expression of gp130 and OSMR-beta, but not of LIFR on these cells. Functionally, OSM upregulated intercellular adhesion molecule-1, but did not induce vascular cell adhesion molecule-1 in HCEC. Further, OSM upregulated IL-6 and monocyte chemoattractant protein (MCP)-1, whereas IL-8 was unaffected. Combined application of tumor necrosis factor (TNF)-alpha and OSM synergistically enhanced IL-6 and MCP-1 production, but downregulated TNF-alpha-induced IL-8. As OSM regulated molecules relevant in inflammatory brain diseases, we investigated its expression in normal and pathological human brains. OSM was detected by immunohistochemistry in brains from multiple sclerosis patients in microglia, reactive astrocytes, and infiltrating leukocytes, whereas in normal brains and noninflammatory neurological diseases. immunoreactivity was absent from the parenchyma. These data suggest that immunoregulatory functions in human cerebral endothelial cells may be a mechanism by which OSM participates in the pathophysiology of inflammatory brain disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / analysis
  • Antigens, CD / genetics
  • Blood-Brain Barrier / physiology*
  • Cells, Cultured
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / genetics
  • Cytokine Receptor gp130
  • Endothelium, Vascular / chemistry*
  • Endothelium, Vascular / cytology
  • Female
  • Flow Cytometry
  • Gene Expression / immunology
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / analysis
  • Interleukin-6 / genetics
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Male
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology*
  • Oncostatin M
  • Peptides / analysis*
  • Peptides / genetics
  • RNA, Messenger / analysis
  • Receptor, Ciliary Neurotrophic Factor / genetics
  • Receptors, Cytokine / analysis
  • Receptors, Cytokine / genetics
  • Receptors, Interleukin-6 / genetics
  • Receptors, OSM-LIF
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / immunology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antigens, CD
  • Chemokine CCL2
  • IL6ST protein, human
  • Interleukin-6
  • LIFR protein, human
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Membrane Glycoproteins
  • OSM protein, human
  • Peptides
  • RNA, Messenger
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Cytokine
  • Receptors, Interleukin-6
  • Receptors, OSM-LIF
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Oncostatin M
  • Intercellular Adhesion Molecule-1
  • Cytokine Receptor gp130