Roles of Rac and cytosolic phospholipase A2 in the intracellular signalling in response to titanium particles

Sang Soo Lee, Chang Hoon Woo, Jun Dong Chang, Jae Hong Kim

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Titanium (Ti) particle is one of the prosthetic materials commonly used in implantation and has frequently been implicated in pathogenesis such as periprosthetic osteolysis. In the present study, we undertook to understand the intracellular signalling pathway stimulated by exogenous Ti at Rat-2 fibroblasts. By reporter gene analysis following transient transfections, exogenous Ti was shown to stimulate c-fos serum response element (SRE)-dependent luciferase activities in a dose-dependent manner. In addition, Ti-induced SRE activation was shown to be dramatically repressed by RacN17, a dominant negative mutant of Rac1, suggesting that Rac GTPase is essential for the signalling of Ti to c-fos SRE. Furthermore, pretreatment with MAFP, an inhibitor of cytosolic phospholipase A2 (cPLA2), MK886, an inhibitor of 5-lipoxygenase (5-LO), or indomethacin, a general inhibitor of cyclooxygenase (COX), also significantly repressed Ti-induced SRE activation, suggesting mediatory roles of cPLA2 and subsequent arachidonic acid (AA) metabolisms to leukotrienes (LTs) and prostaglandins (PGs) in the Ti signalling to c-fos SRE. Consistent with these results, intracellular levels of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were Rac-dependently elevated in cells exposed to Ti particles.

Original languageEnglish
Pages (from-to)339-345
Number of pages7
JournalCellular Signalling
Volume15
Issue number3
DOIs
Publication statusPublished - 2003 Mar 1

Bibliographical note

Funding Information:
This work was supported by grants (RO2-2002-000-00029-0) from the Basic Research Program, Interdisciplinary Research Program (1999-2-207-004-5), SRC (Aging and Apoptosis Research Center) Fund (2002) to Seoul National University (Medical School) of the Korea Science and Engineering Foundation and Brain Korea 21 (BK21) program. We wish to thank Dr. A. Hall (University College, London, England) for providing us with RacN17 expression plasmid.

Keywords

  • LTB
  • PGE
  • PLA
  • Rac
  • Titanium
  • c-fos SRE

ASJC Scopus subject areas

  • Cell Biology

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