TY - JOUR
T1 - Brain microvessel endothelial cell responses to tumor necrosis factor-alpha involve a nuclear factor kappa B (NF-κB) signal transduction pathway
AU - Trickler, W. J.
AU - Mayhan, W. G.
AU - Miller, D. W.
N1 - Funding Information:
This work was supported by PHS grant R29-NS-36831 (DWM) and NIH grant HL-40781 (WGM).
PY - 2005/6/28
Y1 - 2005/6/28
N2 - 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.
AB - 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.
KW - Blood-brain barrier
KW - Cyclooxygenase 2
KW - Nuclear factor kappa B
KW - Tumor necrosis factor-alpha
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U2 - 10.1016/j.brainres.2005.04.028
DO - 10.1016/j.brainres.2005.04.028
M3 - Article
C2 - 15916752
AN - SCOPUS:20444398140
VL - 1048
SP - 24
EP - 31
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -