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An accessory role for ceramide in interleukin-1β induced prostaglandin synthesis

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Abstract

Interleukin-1β (IL-1) is a potent inducer of prostaglandin E2 (PGE2) synthesis. We previously showed that ceramide accumulates in fibroblasts treated with IL-1 and that it enhances IL-1-induced PGE2 production. The present study was undertaken to determine the mechanism(s) by which ceramide and IL-1 interact to enhance PGE2 production by examining their respective effects on the rate-limiting enzymes in PGE2 synthesis, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2). IL-1-induced PGE2 synthesis required ω8 h even though COX-1 was constitutively expressed (both mRNA and protein) and enzymatically active in untreated cells. Conversely, COX-2 mRNA was barely detectable in untreated cells but within 2 h, ceramide or IL-1 alone induced a 5 and 20 fold increase in COX-2 mRNA, respectively. However, IL-1 induced COX-2 protein synthesis was only detectable 6-7 h after maximal COX-2 mRNA induction; COX-2 protein accumulation was not induced by ceramide alone. Ceramide however, reduced the length of time required for IL- 1 to induce COX-2 protein accumulation and increased COX-2 protein accumulation. IL-1 induced a 15 fold increase in COX-1 mRNA including an alternatively spliced form of COX-1. IL-1, but not ceramide induced cPLA2 mRNA and protein expression which corresponded with the initiation of PGE2 synthesis. These observations indicate that, (1) while either ceramide or IL-1 rapidly induced COX-2 mRNA, COX-2 protein only accumulated in IL- 1 treated cells after a delay of 6-7 h, (2) IL-1-induced PGE2 synthesis required both COX-2 and cPLA2 protein synthesis and, (3) ceramide enhanced (temporally and quantitatively) IL-1-induced COX-2 protein accumulation resulting in enhanced PGE2 production.

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Authors and Affiliations

  1. The Department of Veterans Affairs Medical Center, The University of Tennessee, Memphis, TN, 38163, USA

    Kanyawim Kiritikara, Rajendra Raghow & Leslie R. Ballou

  2. Department of Medicine, The University of Tennessee, Memphis, TN, 38163, USA.

    Stanley J. F. Laulederkind, Takuro Kanekura & Leslie R. Ballou

  3. Department of Pharmacology, College of Medicine, The University of Tennessee, Memphis, TN, 38163, USA

    Rajendra Raghow

  4. Department of Biochemistry, The University of Tennessee, Memphis, TN, 38163, USA

    Leslie R. Ballou

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  1. Kanyawim Kiritikara
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  3. Rajendra Raghow
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  4. Takuro Kanekura
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  5. Leslie R. Ballou
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Kiritikara, K., Laulederkind, S.J.F., Raghow, R. et al. An accessory role for ceramide in interleukin-1β induced prostaglandin synthesis. Mol Cell Biochem 181, 41–48 (1998). https://doi.org/10.1023/A:1006824009546

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