Independent arachidonic acid-mediated gene regulatory pathways in lymphocytes.

In the BW5147 T cell line, we have identified two independent regulatory pathways by which arachidonic acid (20:4) can alter gene expression. The inhibitory effect of 20:4 upon stearoyl-CoA desaturase 2 (SCD2) gene expression was seen to be independent of oxidation of 20:4 by either the lipoxygenase or cyclooxygenase pathways. Moreover, oxidized metabolites of 20:4 (15-HPETE and 15-HETE) failed to diminish SCD2 mRNA accumulation whereas 20:4 itself was effective in completely suppressing SCD2 gene expression. In contrast, the transcriptional induction of the proto-oncogene c-fos was dependent upon the oxidation of 20:4 by the lipoxygenase pathway. By using the protein synthesis inhibitor, cycloheximide, we also show that the 20:4-mediated regulatory effects upon SCD2 or c-fos are completely independent of new protein synthesis. Collectively, the results identify the existence of multiple, independent, intracellular 20:4-mediated regulatory pathways operating simultaneously within this cell type.