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

Kanyawim Kirtikara, Stanley J.R. Laulederkind, Rajendra Raghow, Takuro Kanekura, Leslie R. Ballou

Research output: Contribution to journalArticle

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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 ≃ 8 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 cPLA, 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 cPLA, protein synthesis and, (3) ceramide enhanced (temporally and quantitatively) IL-1-induced COX-2 protein accumulation resulting in enhanced PGE2 production.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume181
Issue number1-2
DOIs
StatePublished - Apr 1 1998

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Ceramides
Accessories
Interleukin-1
Prostaglandins
Cyclooxygenase 2
Dinoprostone
Cyclooxygenase 1
Messenger RNA
Proteins
Cytosolic Phospholipases A2
Fibroblasts

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

An accessory role for ceramide in interleukin-1β induced prostaglandin synthesis. / Kirtikara, Kanyawim; Laulederkind, Stanley J.R.; Raghow, Rajendra; Kanekura, Takuro; Ballou, Leslie R.

In: Molecular and Cellular Biochemistry, Vol. 181, No. 1-2, 01.04.1998, p. 41-48.

Research output: Contribution to journalArticle

Kirtikara, Kanyawim ; Laulederkind, Stanley J.R. ; Raghow, Rajendra ; Kanekura, Takuro ; Ballou, Leslie R. / An accessory role for ceramide in interleukin-1β induced prostaglandin synthesis. In: Molecular and Cellular Biochemistry. 1998 ; Vol. 181, No. 1-2. pp. 41-48.
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