|
|
Differential
effects of prostaglandin derived from omega -6 and omega -3 polyunsaturated
fatty acids on COX-2 expression and IL-6 secretion
Bagga
D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST
Divisions
of Hematology-Oncology and Gynecologic Oncology, Department of Obstetrics and
Gynecology, Division of Cardiology, Department of Medicine, and Department of
Molecular and Medical Pharmacology, University of California, Los Angeles, CA
90095-1679
Omega-6
(omega-6) polyunsaturated fatty acids (PUFA), abundant in the Western diet, are
precursors for a number of key mediators of inflammation including the 2-series
of prostaglandins (PG).
PGE(2), a cyclooxygenase (COX) metabolite of arachidonic acid, a omega-6 PUFA,
is a potent mediator of inflammation and cell proliferation.
Dietary supplements rich in omega-3 PUFA reduce the concentrations of 2-series
PG and increase the synthesis of 3-series PG (e.g., PGE(3)), which are believed
to be less inflammatory.
However, studies on cellular consequences of increases in 3-series PG in
comparison to 2-series PG have not been reported.
In this study, we compared the effects of PGE(2) and PGE(3) on
(i) cell proliferation in NIH 3T3 fibroblasts,
(ii) expression and transcriptional regulation of the COX-2 gene in NIH 3T3
fibroblasts, and
(iii) the production of an inflammatory cytokine, IL-6, in RAW 264.7
macrophages.
PGE(3),
unlike PGE(2), is not mitogenic to NIH 3T3 fibroblasts.
PGE(2) and PGE(3) both induce COX-2 mRNA via similar signaling mechanisms;
however, compared with PGE(2), PGE(3) is significantly less efficient in
inducing COX-2 gene expression.
Furthermore, although both PGE(2) and PGE(3) induce IL-6 synthesis in RAW 264.7
macrophages, PGE(3) is substantially less efficient compared with PGE(2).
We further show that increasing the omega-3 content of membrane phospholipid
results in a decrease in mitogen-induced PGE(2) synthesis.
Taken together, our data suggest that successful replacement of omega-6 PUFA
with omega-3 PUFA in cell membranes can result in a decreased cellular response
to mitogenic and inflammatory stimuli.
PMID: 12578976 [PubMed -
indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12578976&dopt=Abstract
|
