PT  - JOURNAL ARTICLE
AU  - K G Mugridge
AU  - D Donati
AU  - S Silvestri
AU  - L Parente
TI  - Arachidonic acid lipoxygenation may be involved in interleukin-1 induction of prostaglandin biosynthesis.
DP  - 1989 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 714--720
VI  - 250
IP  - 2
4099  - http://jpet.aspetjournals.org/content/250/2/714.short
4100  - http://jpet.aspetjournals.org/content/250/2/714.full
SO  - J Pharmacol Exp Ther1989 Aug 01; 250
AB  - The induction of prostaglandin (PG) biosynthesis by human recombinant interleukin-1 beta (hrIL-1 beta) has been investigated using rat-isolated stomach strip preparations. hrIL-1 beta (30 and 120 pM) increased CaCl2 responses in a dose-dependent manner with both concentrations significantly potentiating maximum contraction (62.4 +/- 5.1 and 184.2 +/- 36.9%, respectively). This enhancement was characterized further using inhibitors of arachidonic acid metabolism, mRNA and protein synthesis as well as a selective leukotriene (LT) D4 antagonist. Indomethacin (5.6 microM) reduced CaCl2 contractions in the presence of hrIL-1 beta (30 pM) such that only a small residual response was evident, this being reduced further by NDGA (20 microM). Contrastingly, nordihydljroguaiaretic acid reduced only the enhancement of response due to hrIL-1 beta. These findings, supported by parallel radio-immunoassay of PGE2 in the bathing medium after drug treatments suggest strongly that the augmentation of contraction by hrIL-1 beta is due mainly to increased production of PGs. Furthermore, this enhancement is inhibited in a dose-dependent manner by the LTD4 antagonist FPL55712. Additionally, using actinomycin-D and cycloheximide we demonstrated that the hrIL-1 beta induced potentiation is dependent upon mRNA and protein biosynthesis as both compounds substantially reduced responses in the presence of the interleukin. These results provide possible evidence that hrIL-1 beta induced PG production is mediated by a lipoxygenase product, most likely LTD4, which in turn could be important for the induction of de novo protein synthesis.