Modulation of macrophage tumor necrosis factor-alpha production by omega-3 polyunsaturated fatty acids, eicosanoids, and calcium
Chen, Steven Enchi
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/21361
Description
Title
Modulation of macrophage tumor necrosis factor-alpha production by omega-3 polyunsaturated fatty acids, eicosanoids, and calcium
Author(s)
Chen, Steven Enchi
Issue Date
1993
Doctoral Committee Chair(s)
Erdman, John W.
Department of Study
Food Science and Human Nutrition
Discipline
Food Science and Human Nutrition
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Agriculture, Food Science and Technology
Health Sciences, Immunology
Language
eng
Abstract
This research was undertaken to investigate the suppression of tumor necrosis factor-$\alpha$ (TNF-$\alpha)$ production imparted by $\omega$-3 fatty acid (FA) enhancement on macrophage (m$\phi).$ In an in vitro system, murine monocytic cell lines and peritoneal m$\phi$ were incubated with either eicosapentaenoate-BSA (EPA, $\omega$-3), arachidonate-BSA (ARA, $\omega$-6), palmitoleate-BSA (PMOA, $\omega$-7), or BSA. EPA consistently caused $>$60% suppression of LPS-induced TNF-$\alpha$ synthesis. PMOA and BSA had no effect. Recombinant murine interferon-$\gamma$ (rMulFN-$\gamma)$ enhanced lipopolysaccharide (LPS)-induced TNF-$\alpha$ production and dose-dependently reduced the suppression caused by EPA. Indomethacin augmented TNF-$\alpha$ production; however, it did not completely abrogate the EPA-induced suppression. ARA caused suppression similar to EPA, but this was totally abrogated by indomethacin. The Ca$\sp{2+}$ ionophore ionomycin was effective as a priming agent and abrogated the EPA-induced suppression when used with LPS.
Eicosanoids derived from ARA (PGE$\sb2)$ and EPA (PGE$\sb3)$ are structurally different. Both PGE$\sb2$ and PGE$\sb3$ dose-dependently suppressed TNF-$\alpha.$ Their efficacy was dependent on concentration and the level of m$\phi$ stimulation, in the absence or presence of indomethacin.
TNF-$\alpha$ mRNA levels of control and EPA-enhanced groups were compared. When IFN-$\gamma$ was used, the mRNA levels of EPA-treated groups were equal in magnitude to the control groups'. Therefore, the observed suppression at the cellular level could not be attributed to differential levels of mRNA accumulation at low activational states. When ionomycin was used as a priming agent, the mRNA levels for the EPA group was consistently higher than that of the controls', which, at the cellular level, was paralleled with abrogation of the differences in TNF-$\alpha$ detected between groups. Together, the findings suggested that post-transcriptional processes were responsible for the observed suppression of TNF-$\alpha.$
From these findings, $\omega$-3 FA enhancement of murine m$\phi$-induced suppression of TNF-$\alpha$ by a minimum of two paths. First, PGE$\sb3$ derived from EPA could directly cause suppression of TNF-$\alpha.$ Second, ionomycin, IFN-$\gamma$ and PKc activation demonstrated that up-regulation of this pathway could reverse the effects of $\omega$-3 FA enhancement.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
