Interleukin 1beta induces functional prostaglandin E synthase in cultured human umbilical vein endothelial cells

• Autorzy: Uracz W. , Uracz D. , Olszanecki R. , Gryglewski R.J.
• Języki publikacji: EN

Abstrakty

EN

Prostaglandin endoperoxide H2 (PGH2) is generated from arachidonic acid by either constitutive (COX-1) or inducible (COX-2) cyclooxygenases. In arterial wall PGH2 is converted by PGI2 synthase (PGI-S) to prostacyclin (PGI2), and in platelets by thromboxane synthase (TX-S) to thromboxane (TXA2). Other prostanoids as PGD2, PGF2alpha or PGE2 were believed to arise non-enzymatically from PGH2. Only recently, human prostaglandin E synthase (PGE-S) has been identified and cloned as a membrane bound, microsomal, glutathione-dependent inducible enzyme. Here we demonstrated that interleukin 1ß (IL-1ß) is an inducer of COX-2 and PGE-S in human umbilical vein endothelial cells (HUVEC). Functional expression of PGE-S was measured at the level of specific mRNA by semi-quantitative RT-PCR, PGE-S protein was detected by Western blot in HUVEC, while PGE2 was measured by immunoassay in the supernatant. Actinomycin D, a classical transcription inhibitor, was used to prove that indeed IL-1ß induced the functional PGE-S enzyme. PGE2 generation in HUVEC was inhibited by indomethacin, acetamoniphen and dexamethasone. In conclusion, we found that in cultured endothelial cells IL-1ß induced as evidenced by the appearance of its transcript and its functional enzyme. The induction of endothelial PGE-S and COX-2 appeared to be and their transcripts were induced as fast as one might expect from immediate early genes. It means that IL-1ß-triggered-PGE2 biosynthesis in endothelial cells is probably regulated by induction of both COX-2 and PGE-S. This is way we hypothesise the existence of at least two distinct pools of COX-2: the first selectively coupled to PGE-S and the second one that is coupled to PGI-S yielding the main endothelial product - PGI2.

Słowa kluczowe

EN

umbilical vein; interleukin 1beta; gene expression; endothelial cell; prostaglandin E; cyclooxygenase

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2002
• Tom: 53
• Numer: 4,1
• Opis fizyczny: p.643-654,fig.

Twórcy

autor

Uracz W.

• Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Krakow, Poland

autor

Uracz D.

autor

Olszanecki R.

autor

Gryglewski R.J.