Protein-tyrosine-kinase-dependent expression of cyclo-oxygenase-1 and -2 mRNAs in human endothelial cells

Abstract

Endothelial cells possess constitutive or inducible cyclo-oxygenase (COX) isoenzymes for prostacyclin production, but the mechanisms for their expression are largely unknown. We found that vanadate, an inhibitor of protein-tyrosine phosphatases, induced the expression of two COX isoenzyme mRNAs in human umbilical vein endothelial cells (HUVEC) in a time- and dose-dependent manner. Vanadate also stimulated an increase in COX-2 protein levels, but did not affect significantly the levels of constitutively expressed COX-1 protein. Synergistic enhancement of expression of the two COX isoenzyme mRNAs was observed on stimulation of HUVEC with vanadate plus interleukin-1alpha. Tyrphostin-47, which as an inhibitor of protein-tyrosine kinases abolished vanadate-induced protein-tyrosine phosphorylation, inhibited expression of the two COX isoenzyme mRNAs in HUVEC stimulated with vanadate or interleukin-1alpha. These data provide conclusive evidence that activation of protein-tyrosine kinases is causally linked to expression of the mRNAs for the two COX isoenzymes in HUVEC.

Involvement of ERK and Protein Tyrosine Phosphatase Signaling Pathways in EGCG-Induced Cyclooxygenase-2 Expression in Raw 264.7 Cells

“…These finding suggest that EGCG treatment may activate these transcriptional factors through ERK signaling pathway, leading to COX-2 expression and subsequent PGE 2 production. In addition, a role for protein-tyrosine kinases (PTKs) in control of COX-2 expression was also reported for interleukin-1␣ treated human endothelial cells (31). Synergistic enhancement of expression of the COX-2 expression was observed on stimulation of Raw264.7 with vanadate plus EGCG.…”

Ultraviolet irradiation induces cyclooxygenase-2 expression in keratinocytes

“…The role of tyrosine kinases in the expression of COX-2 has also been shown in other cell types. 17,18 Surprisingly, sodium orthovanadate was able to inhibit COX-2 induction by UVB irradiation. The reason for this is presently unknown.…”

Localisation of High Acid Phosphotyrosine Phosphatase Activity in Afferent Arterioles and Glomeruli of Human Kidney

“…induction by antigen receptors (Jin et al 1998, Dawson et al 2000, Barat & Tremblay 2003 or by vasoactive substances, growth factors, and cytokines (Stroebel & Goppelt-Struebe 1994, Rzymkiewicz et al 1995, Wenzel et al 1995, Hirai et al 1997. Furthermore, these results showed that PTK activity was necessary for PTP inhibitor-induced events.…”

“…CsA depresses this pathway by inhibiting calcineurin (Shaw et al 1995). Indirect evidence suggests that PTPs are also linked with the CsAsensitive calcineurin signal pathway in endothelial and mesangial cells because these cells possess inducible cyclooxygenase-2 and induction is achieved both with PTP inhibitors (Stroebel & Goppelt-Struebe 1994, Hirai et al 1997) and vascular endothelial growth factor or endothelin-1, and the latter inductions are mediated via the CsA-sensitive calcineurin signal pathway (Herna´ndez et al 2001, Sugimoto et al 2001. The direct effect of clinically effective CsA concentrations on cellular PTP activity seems unlikely because CsA did not influence the activity of lymphocytic or endothelial and mesangial phosphotyrosine phosphatase, although the concentration used was about 100 times greater than necessary for effective immunosuppression (Bautiuk et al 1997).…”