Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-10-17
pubmed:abstractText
Wear particles are believed to induce periprosthetic inflammation which contributes to periprosthetic osteolysis. TNFalpha plays a pivotal role in the pathogenesis of this process. The molecular mechanisms leading to the development of periprosthetic inflammation with upregulated TNFalpha expression in monocytic cells in response to different wear particles have yet to be defined. In this study we evaluated the effects of polyethylene- and TiAlV-particles on activation of NF-kappaB signalling pathways and TNFalpha biosynthesis and release in monocytic cells with respect to periprosthetic osteoclastogenesis. THP-1 monocytic cells were differentiated to macrophage-like cells and exposed to LPS-detoxified polyethylene and prosthesis-derived TiAlV-particles. TNFalpha release was analyzed in culture supernatant by ELISA. NF-kappaB activation was examined by electrophoretic mobility shift assay (EMSA), and NF-kappaB target promoter activities including transactivation of the TNFalpha promoter were determined by luciferase reporter gene assays. Differentiated THP-1 macrophages were exposed to increasing numbers of particles for 0, 60, 180 and 360 min. Both, polyethylene- and TiAlV-particles induced a significant activation of both NF-kappaB and TNFalpha promoters at 180 min. A significant TNFalpha release was detected after 360 min exposure to polyethylene- and TiAlV-particles in a dose dependent manner. In comparison, LPS induced a much greater activation of NF-kappaB and TNFalpha promoters, and TNFalpha secretion into the supernatant was strongly induced. These results provide evidence that induction of the NF-kappaB signal transduction pathway in macrophages plays a major role in initiating and mediating the inflammatory response leading to periprosthetic osteolysis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0736-0266
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1241-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Activation of NF-kappaB signalling and TNFalpha-expression in THP-1 macrophages by TiAlV- and polyethylene-wear particles.
pubmed:affiliation
Department of Orthopaedic Surgery, Julius-Maximilians University Würzburg, König-Ludwig-Haus, Brettreichstrasse 11, D-97074 Würzburg, Germany. b-baumann.klh@mail.uni-wuerzburg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't