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Abstract

Arachidonic acid lipoxygenation may be involved in interleukin-1 induction of prostaglandin biosynthesis.

K G Mugridge, D Donati, S Silvestri and L Parente
Journal of Pharmacology and Experimental Therapeutics August 1989, 250 (2) 714-720;
K G Mugridge
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D Donati
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S Silvestri
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L Parente
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Abstract

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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 250, Issue 2
1 Aug 1989
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Abstract

Arachidonic acid lipoxygenation may be involved in interleukin-1 induction of prostaglandin biosynthesis.

K G Mugridge, D Donati, S Silvestri and L Parente
Journal of Pharmacology and Experimental Therapeutics August 1, 1989, 250 (2) 714-720;

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Abstract

Arachidonic acid lipoxygenation may be involved in interleukin-1 induction of prostaglandin biosynthesis.

K G Mugridge, D Donati, S Silvestri and L Parente
Journal of Pharmacology and Experimental Therapeutics August 1, 1989, 250 (2) 714-720;
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