Effects of unsaturated fatty acids on expression of early response genes in human T lymphocytes.
Administration of gamma-linolenic acid, which is converted rapidly to dihomo-gamma-linolenic acid (DGLA), reduces joint swelling and tenderness in patients with rheumatoid arthritis. Joint tissue inflammation in patients with rheumatoid arthritis is due in part to activation of T lymphocytes. DGLA suppresses T cell activation and production of interleukin-2 (IL-2). The protooncogenes c-myc and c-fos are early response genes which are critical to regulation of T cell proliferation. We therefore examined the effects of gamma-linolenic acid and other unsaturated fatty acids on c-myc and c-fos expression by means of the polymerase chain reaction and Northern blotting. IL-2 production by the human T cell line Jurkat is dependent on a fall in mRNA for c-myc and a rise in mRNA for c-fos. The data presented here indicate that reduction of steady-state levels of mRNA for c-myc and rises in steady-state levels of mRNA for c-fos are both reduced markedly in cells incubated with DGLA. Cells incubated with arachidonic acid, eicosapentaenoic acid or oleic acid exhibit more modest changes in expression of these early response genes.
Williams
W V
WV
Rheumatology Division, University of Pennsylvania School of Medicine, Philadelphia 19104-6100, USA.
Rosenbaum
H
H
Zurier
R B
RB
D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D016762:Genes, fos / Q000187:drug effects* / Q000235:genetics*; D016259:Genes, myc / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D017965:gamma-Linolenic Acid / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D011453:Prostaglandins; D012333:RNA, Messenger; D017965:gamma-Linolenic Acid; D015126:8,11,14-Eicosatrienoic Acid