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Arachidonic acid metabolism in TNF, CD178 (CD95 ligand) and ceramide-mediated cytotoxicity

Author(s): Monika Ołdak | Jarosław Joźwiak | Radosław Maksym | Jacek Malejczyk

Journal: Archives of Medical Science
ISSN 1734-1922

Volume: 3;
Issue: 1;
Start page: 27;
Date: 2007;
Original page

Keywords: arachidonic acid | TNF | CD178 | CD95 | ceramide

Introduction: Arachidonic acid release has been reported to play a significant role in TNF-induced cytotoxicity. However, the role of this signalling cascade in CD178-(CD95 ligand)mediated cytotoxicity remains unclear. The aim of the study was to investigate the role of arachidonic acid metabolism in TNF- and CD95-mediated cytotoxicity. Material and methods: Naturally TNF-sensitive A9 and CD178-sensitive A9-CD95 (the cells stably transfected with human CD95) cell lines were subjected to inhibitors of phospholipase A2 (AACOCF3, PACOCF3), lipoxygenase (NDGA) and cycloxygenase (indomethacin). Results: We showed that the cytotoxic activity of TNF could by inhibited by AACOCF3 and PACOCF3, inhibitors of phospholipase A2 as well as by NDGA, displaying anti-lipoxygenase and anti-oxidant inhibitory activity. In contrast, none of the tested inhibitors of arachidonic acid metabolism affected CD178-mediated cytotoxicity in A9-CD95 cells stably expressing CD95. Cytotoxicity mediated by C6-ceramide, a possible mediator of TNF- and CD178-mediated cytotoxicity, was also unaffected by these inhibitors. Conclusions: The above facts strongly suggest that CD95- as well as C6 ceramide-induced cell death does not depend on arachidonic acid metabolism.
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