Brain microvessel endothelial cell responses to tumor necrosis factor-alpha involve a nuclear factor kappa B (NF-κB) signal transduction pathway

W. J. Trickler, William Mayhan, D. W. Miller

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The involvement of nuclear factor kappa B (NF-κB) in TNF-induced increases in cerebral microvascular permeability was evaluated both in vitro, using primary cultured bovine brain microvessel endothelial cells (BBMEC), and in vivo, using the rat cranial window model. In primary cultured BBMEC, TNF exposure resulted in an increased appearance of the Rel A subunit of NF-κB in immunoblots of cell lysates. Increases in the Rel A subunit of NF-κB were observed as early as 30-min after administration of TNF. The increased permeability and the secretion of prostaglandin E2 in response to TNF exposure in BBMEC monolayers were significantly reduced by several different NF-κB inhibitors, including PDTC, CAPE, BAY 11-7085, and lactacystin. Similar results were also obtained in the rat cranial window model where treatment with the COX-2 inhibitor, NS-398 (0.1 μM), or the NF-κB inhibitor, PDTC (10μM), significantly reduced the permeability increases produced by TNF. These studies suggest that the increases in BBB permeability following TNF exposure are attributable to activation of an NF-κB-mediated signaling pathway in the cerebral microvasculature.

Original languageEnglish (US)
Pages (from-to)24-31
Number of pages8
JournalBrain Research
Volume1048
Issue number1-2
DOIs
StatePublished - Jun 28 2005

Fingerprint

NF-kappa B
Microvessels
Signal Transduction
Endothelial Cells
Tumor Necrosis Factor-alpha
Brain
Permeability
Cyclooxygenase 2 Inhibitors
Capillary Permeability
Dinoprostone

Keywords

  • Blood-brain barrier
  • Cyclooxygenase 2
  • Nuclear factor kappa B
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Brain microvessel endothelial cell responses to tumor necrosis factor-alpha involve a nuclear factor kappa B (NF-κB) signal transduction pathway. / Trickler, W. J.; Mayhan, William; Miller, D. W.

In: Brain Research, Vol. 1048, No. 1-2, 28.06.2005, p. 24-31.

Research output: Contribution to journalArticle

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