Expression of inflammatory cytokines and adhesion molecules in cultured endothelial cells exposed to arachidonic acid

Simone Kaiser, Bernhard Hennig, Valerie Young, Michal Toborek

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammatory response and the release of inflammatory cytokines, including tumor necrosis factor-α (TNF), appear to be integral parts in the initial steps of atherogenesis. Among different cellular effects, TNF activates phospholipase A2 and thus releases arachidonic acid (AA) from the cellular membranes. AA may significantly contribute to the inflammatory response of the endothelium. To test this hypothesis, cellular oxidative stress, inflammatory cytokines, such as interleukin 1β and interleukin 8, as well as adhesion molecules, such as VCAM-1 and ICAM-1, were measured in human umbilical vein endothelial cells (HUVEC) exposed to 90 or 180 μM of AA. Because AA is actively metabolized by cyclooxygenase or lipoxygenase, the experiments were performed in the presence or absence of inhibitors of these enzymes, indomethacin or nordihydroguaiaretic acid (NDGA), respectively. AA induced cellular oxidation in time and concentration-dependent patterns. In addition, AA increased production of inflammatory cytokines and adhesion molecules in HUVEC. These cellular responses were potentiated in the presence of indomethacin or NDGA and, in particular, when both cyclooxygenase or lipoxygenase pathways were inhibited. Moreover, AA disrupted endothelial barrier function, as measured by albumin transfer across endothelial monolayers. These results suggest that the release of AA from cellular membranes may be an important mechanism in the induction of the inflammatory response and endothelial cell dysfunction.

Original languageEnglish (US)
Pages (from-to)A303
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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