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URN: urn:nbn:de:bsz:291-scidok-14946
URL: http://scidok.sulb.uni-saarland.de/volltexte/2008/1494/


The tyrosine kinase Pyk2 mediates lipopolysaccharide-induced IL-8 expression in human endothelial cells

Anand, Appakkudal R. ; Cucchiarini, Magali ; Terwilliger, Ernest F. ; Ganju, Ramesh K.

Quelle: (2008) The journal of immunology. - 180. 2008, 8, S. 5636-5644
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Dokument 1.pdf (357 KB)

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Institut: Fachrichtung 2.16 - Orthopädie
DDC-Sachgruppe: Medizin
Dokumentart: Aufsatz
Sprache: Deutsch
Erstellungsjahr: 2008
Publikationsdatum: 18.04.2008
Kurzfassung auf Englisch: Secretion of proinflammatory cytokines by LPS activated endothelial cells contributes substantially to the pathogenesis of sepsis. However, the mechanism involved in this process is not well understood. In the present study, we determined the role of a nonreceptor proline-rich tyrosine kinase, Pyk2, in LPS-induced IL-8 (CXCL8) production in endothelial cells. First, we observed a marked activation of Pyk2 in response to LPS. Furthermore, inhibition of Pyk2 activity in these cells by transduction with the catalytically inactive Pyk2 mutant, transfection with Pyk2-specific small interfering RNA, or treatment with Tyrphostin A9 significantly blocked LPS-induced IL-8 production. The supernatants of LPS-stimulated cells exhibiting attenuated Pyk2 activity
blocked transendothelial neutrophil migration in comparison to the supernatants of LPS-treated controls, thus confirming the inhibition of functional IL-8 production. Investigations into the molecular mechanism of this pathway revealed that LPS activates Pyk2 leading to IL-8 production through the TLR4. In addition, we identified the p38 MAPK pathway to be a critical step downstream of Pyk2 during LPS-induced IL-8 production. Taken together, these results demonstrate a novel role for Pyk2 in LPS-induced IL-8 production in endothelial cells.

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