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Chemokine IL‐8 induction by particulate wear debris in osteoblasts is mediated by NF‐κB
Author(s) -
Fritz Elizabeth A.,
Jacobs Joshua J.,
Glant Tibor T.,
Roebuck Kenneth A.
Publication year - 2005
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1016/j.orthres.2005.03.013.1100230603
Subject(s) - chemokine , mapk/erk pathway , microbiology and biotechnology , chemotaxis , signal transduction , p38 mitogen activated protein kinases , interleukin 8 , chemistry , nf κb , osteoblast , inflammation , biology , immunology , receptor , in vitro , biochemistry
Chemokines, or chemotactic cytokines, are major regulators of the inflammatory response and have been identified as pathogenic factors in the periprosthetic soft tissue. Particulate wear debris induced NF‐kB activation, the major transcriptional regulator of IL‐8 and MCP‐1 pro‐inflammatory genes and, indeed, both IL‐8 and MCP‐1 chemokine gene expressions were upregulated in titanium particulate‐stimulated human osteoblasts. Here, we demonstrate that phagocytosed particles activate the IL‐8 gene promoter via a NF‐kB‐mediated mechanism. Transfection of a dominant negative mutant IkBα protein that cannot be serine phosphorylated led to suppression of IL‐8 promoter activity. The p65/RelA NF‐kB subunit activity was affected in both a time‐ and titanium particle concentration‐dependent fashion. Titanium particles led to increased ERK, JNK, and p38 activation in MG‐63 osteoblast cells, and IL‐8 protein release was suppressed by specific inhibitors of the ERK and p38 MAPK pathways. Together, our results suggest that wear debris particles induce chemokine expression in osteoblasts via NF‐kB‐mediated transcriptional activation, which is controlled by the MAPK signal transduction pathway. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.