Author/Editor		Hribar, Maruša
Title		Vpliv tumor nekroznega faktorja alfa na mikrovascularne endotelne celice
Translated title		Activities of tumor necrosis factor-alpha on microvascular endothelial cells
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		1999
Volume		str. 104
Language		slo
Abstract		Tumor necrosis factor (TNF) is a pro-inflammatory cytokine, mainly produced by activated macrophages, that has both TNF receptor-dependent and TNF receptor independent adivities. Microvascular endothelial cells (MVEC) represent major target cells for the tumor necrotic adivity of TNF, as well as in pathological conditions associated with TNF overexpression, such as acute respiratory distress syndrome and cerebral malaria. We investigated the conditions under which TNF induces apoptosis in MVEC. We found that these cells, upon 72 h of incubation, become sensitive to TNF cytotoxicity, provided that they are at confluence. Altematively, when MVEC are transcriptionally inhibited, they undergo apoptosis upon TNF treatment already after 18 h, even in sub-confluent conditions.Since MVEC express both TNFR1 and TNFR2, we were interested to assess the role of each TNF receptor type in cytotoxicity. MVEC isolated from mice genetically deficient in TNFR1 (Tnfr1 o) or TNFR2 (Tnfr2 o) were incubated with TNF in the presence (sensitized cytotoxicity) or absence (dired cytotoxicity) of the transcriptional inhibitor adinomycin D. Under sensitized conditions, TNFR1 was necessary and suffcient for apoptosis indudion. In contrast, both TNF receptors were required for direct TNF-mediated cytotoxicity in MVEC. Since TNFR2, in contrast to TNFR1, has no death domain, we further investigated how it could be implicated in apoptosis. Activation of TNFR2 was recently shown to inhibit the expression of the anti-apoptotic protein Bcl-xL in activated T lymphocytes. Based on our results, demonstrating that TNFR2 is implicated in dired, but not in sensitized cytotoxicity of TNF in MVEC, we wanted to study whether overexpression of Bcl-xL could proted against direct TNF cytotoxicity, implicating TNFR2. We found that Bcl-xL overexpressing cells are protected from direct, but not from sensitized TNF cytotoxicity in MVEC. (Abstract truncated at 2000 characters).
Descriptors		TUMOR NECROSIS FACTOR ENDOTHELIUM, VASCULAR RECEPTORS, TUMOR NECROSIS FACTOR APOPTOSIS DACTINOMYCIN PATCH-CLAMP TECHNIQUES