TGFβ-medlatod regulation of TNFa, IFNy and IL-1β induced MCP-1 expression in human endothelial cells and astrocytes

J. M. Welss, C. A. Cuff, Joan W. Berman

Research output: Contribution to journalArticle

Abstract

Facilitated migration of leukocytes into the central nervous system (CNS) contributes to the pathogenesis of CNS inflammatory disease. Monocyte Chemoattractant Protein-1 (MCP-1) is a potent ohemotactic stimulant for monocytes and T cells. To determine the potential cytokine regulators of MCP-1 in the CNS, we examined MCP-1 expression in human endothelial cells (EC) and astrocytes, two cellular components of the blood-brain barrier (BBS). EC and astrocytes were treated with TNFa (100 U/ml), IFNy (200 U/ml) or t-1β (2 U/ml) for 5 and 16 hours and compared with pretreatment or treatment with 1 ng/ml TGFβ. In astrocytes, TNFor IL-1, but not IFN, induced MCP-1 mRNA and protein as determined by Northern analysis and ELISA. TGF cotreatment caused a 70% increase in TNF-induced MCP-1 mRNA (p<0.002) and 75% and 50% increases in IFNinduced MCP-1 mRNA and protein, respectively (p<0.04 each). TGF/IL-1 cotreatment caused a 15% decrease in mRNA as compared to IL-1 alone (p<0.02). TGF pretreatment induced significant increases in protein for all three cytokines. At 10 ng/ml, TGF did not cause the increase observed with TNF or IFN cotreatment. In EC, TNFa, IFNy and IL-1p induced MCP-1 mRNA and protein. TGF cotreatment decreased TNF induced protein (20%;p<0.05) and IL-1 induced mRNA and protein (20%;p<0.05 each). TGF pretreatment significantly increased IFN and IL-1 induced mRNA and protein. These cytokines are present in the CNS and the kinetics of their expression may regulate MCP-1 facilitated leukocyte transmigration across the BBB.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996

Fingerprint

Chemokine CCL2
astrocytes
Endothelial cells
interleukin-1
Interleukin-1
Astrocytes
endothelial cells
Endothelial Cells
Neurology
Messenger RNA
central nervous system
Proteins
proteins
cytokines
Central Nervous System
pretreatment
Cytokines
leukocytes
Leukocytes
Bulletin boards

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

TGFβ-medlatod regulation of TNFa, IFNy and IL-1β induced MCP-1 expression in human endothelial cells and astrocytes. / Welss, J. M.; Cuff, C. A.; Berman, Joan W.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

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