Urokinase induces matrix metalloproteinase-9/gelatinase B expression in THP-1 monocytes via ERK1/2 and cytosolic phospholipase A(2) activation and eicosanoid production

Menshikov, M.; Torosyan, N.; Elizarova, E.; Plakida, K.; Vorotnikov, A.; Parfyonova, Y.; Stepanova, V.; Bobik, A.; Berk, B.; Tkachuk, V.

Авторы: Menshikov Mikhail, Torosyan Narine, Elizarova Eugenia, Plakida Karina, Vorotnikov Alexander, Parfyonova Yelena, Stepanova Victoria, Bobik Alex, Berk Bradford, Tkachuk Vsevolod
Журнал: Journal of Vascular Research
Том: 43
Номер: 5
Год издания: 2006
Издательство: S. Karger AG
Местоположение издательства: Switzerland
Первая страница: 482
Последняя страница: 490
DOI: 10.1159/000095248
Аннотация: Objective: Urokinase-type plasminogen activator (uPA) regulates cell migration and invasion by pericellular proteolysis and signal transduction events. We characterized the mechanisms by which uPA regulates matrix metalloproteinase-9 (MMP9) function in THP-1 monocytes. Methods and Results: In THP-1 monocytes, MMP9 production induced by urokinase was completely inhibited by the ERK1/2 inhibitor, PD98059, but not by the p38 mitogen-activated protein kinase inhibitor, SB202190. A dominant negative MEK1 adenovirus also blocked MMP9 expression. The effect of urokinase was completely suppressed by genistein and by herbimycin A indicating that tyrosine kinase(s) are required for MMP9 production. Bisindolylmaleimide, a protein kinase C (PKC) inhibitor, did not decrease MMP9 expression suggesting that PKC activation is not required. Key roles for cytosolic phospholipase A 2 (PLA2) and eicosanoid production were shown by complete inhibition with methyl arachidonyl fluorophosphonate (an inhibitor of cytosolic PLA2), and indomethacin (a cyclooxygenase inhibitor), with no effect of monoalide, a secretory PLA2 inhibitor. uPA stimulated phosphorylation of cytosolic PLA2. Conclusions: Induction of MMP9 by uPA in THP-1 monocytes is via a pathway involving MEK1-ERK1/2- mediated activation of cytosolic PLA2 and eicosanoid generation. These data suggest important roles for eicosanoids in monocyte migration induced by uPA and MMP9.
Добавил в систему: Ткачук Всеволод Арсеньевич

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Urokinase induces matrix metalloproteinase-9/gelatinase B expression in THP-1 monocytes via ERK1/2 and cytosolic phospholipase A(2) activation and eicosanoid productionстатья

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