Polyenoic fatty acid ratios alter fibroblast collagen production via PGE2 and PGE receptor subtype response.
Previous experiments have shown that dietary n-6 and n-3 polyenoic fatty acids (PFA) have different effects on collagen production, a process that may be related to the formation of prostaglandins (PG). This study tested the hypothesis that fibroblast collagen production could be regulated by different n- 6:n-3 PFA ratios and that the effects were mediated by PGE(2) and altered signaling via the different PGE receptor subtypes. Compared to a bovine serum albumin control, eicosapentaenoic acid (EPA; 20:5 n-3) treated cells significantly (P < 0.05) increased both collagen production and collagen as a percentage of total cellular protein (C-PTP), but arachidonic acid (AA; 20:4 n-6) reduced collagen production and C-PTP. As the amount of AA decreased and that of EPA increased, collagen production and C-PTP increased, especially when ratio of n-6:n-3 PFA was less than 1:1. C-PTP was significantly correlated with the amount of PGE(2) in the medium. AA- or EPA-treated cells produced similar C-PTP when incubated with 10(-6) M indomethacin, a cyclooxygenase inhibitor. Addition of exogenous PGE(2) to cell cultures treated with 10(-6) M indomethacin for 48 hrs decreased C-PTP in both AA and EPA groups. Decreased C-PTP was observed in AA-treated cells exposed to EP1, EP2, and EP4 PGE receptor agonists and in EPA-treated cells exposed to EP2 and EP4 agonists. AA-treated cell responded to activators of cyclic adenosine monophosphate and protein kinase C by decreasing C-PTP, but EPA-treated cells were unresponsive. In conclusion, collagen production in 3T3-Swiss fibroblasts induced by different n-6:n-3 PFA ratios was correlated with PGE(2) production and altered responsiveness and signaling via the different PGE receptor subtypes.
Jia
Yi
Y
Purdue University, Department of Basic Medical Sciences, 625 Harrison Street, West Lafayette, IN 47907-2026, USA.
Turek
John J
JJ
D016475:3T3 Cells; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000032:analysis; D015232:Dinoprostone / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D020033:Protein Isoforms / Q000819:agonists / Q000145:classification / Q000187:drug effects / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000145:classification / Q000187:drug effects / Q000502:physiology*
D005231:Fatty Acids, Unsaturated; D020033:Protein Isoforms; D018078:Receptors, Prostaglandin E; D003094:Collagen; D004247:DNA; D015232:Dinoprostone; D007213:Indomethacin