Several inflammatory mechanisms contribute to atherogenesis. Monocytes (Mo) are crucial cells in the artery wall that produce proatherogenic cytokines such as interleukin-1B and tumor necrosis factor alpha (TNF). Recently, we showed that supplementation with alpha-tocopherol (AT) significantly decreases the release of interleukin-1B from human Mo. The aim of this study was to test the effect of AT on the release of TNF. Human Mo were isolated from 21 subjects at baseline and follow ing AT supplementation (1200 IU/day for 8 wks). AT produced a significant reduction in TNF release from activated Mo (baseline: 14.2±7.67 pg/mg protein vs. supplemented: 4.9±4.65 pg/mg protein, p<0.001). To examine mechanisms by which AT inhibits TNF, we tested the effect of AT (100uM) on protein kinase C (PKC). AT significantly inhibited PKC levels from human Mo and the PKC inhibitor, Calphostin C, had no effect on TNF release from activated Mo. Leukotriene B4 (LTB4), a product of 5-lipoxygenase (5-LO), augments cytokine release from Mo. AT significantly inhibited 5-LO from Mo and the 5-LO inhibitor, MK886, significantly inhibited TNF release from activated Mo. Addition of LTB4 to the system partially resurrected TNF activity to that of activated cells (LPS: 6.9± 1.5 pg/mg protein; LPS+MK886: 1.6±1.2 pg/mg protein; LPS+ MK886+LTB4: 3.4±1.7 pg/mg protein). Thus, in activated human monocytes, AT inhibits TNF release partly by inhibition of 5-LO and other mechanisms are being studied.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology