PMID- 16392133 OWN - NLM STAT- MEDLINE DCOM- 20060810 LR - 20131121 IS - 1549-3296 (Print) IS - 1549-3296 (Linking) VI - 77 IP - 1 DP - 2006 Apr TI - Chemokine gene activation in human bone marrow-derived osteoblasts following exposure to particulate wear debris. PG - 192-201 AB - Particulate wear debris induces the expression of pro-inflammatory cytokine and chemokine genes in various cell types of the periprosthetic region. We have previously reported that titanium particles stimulate the selective induction of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) chemokines in human osteoblast-like osteosarcoma cells. In this study, we characterize the human bone marrow-derived osteoblast chemokine response to titanium particles. We demonstrate that titanium particles result in enhanced IL-8 and MCP-1 protein secretion as well as differential chemokine gene activation. Osteoblast chemokine expression was regulated at the level of gene transcription, with a time-dependent induction of NF-kappaB activation. Inhibition studies with N-acetyl-L-cysteine (Nac) and MG-132 suggest that titanium particle activation of NF-kappaB activity and IL-8 chemokine expression involves oxidant signaling and IkappaBalpha-proteasomal degradation. Activation of the NF-kappaB transcription factor, as well as the IL-8 gene, are redox-regulated. We also demonstrate that while cytochalasin D, a potent inhibitor of phagocytosis, suppressed the titanium particle effect on IL-8 protein release in human bone marrow-derived osteoblasts, the inhibitor had no effect on IL-8 expression in MG-63 osteoblast-like cells. Collectively, these results provide insight into the potential mechanisms responsible for the particulate activation of osteoblast chemokine expression and suggest an important role for the osteoblast in the pathogenesis of periprosthetic osteolysis. CI - (c) 2005 Wiley Periodicals, Inc. FAU - Fritz, Elizabeth A AU - Fritz EA AD - Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois 60612, USA. FAU - Glant, Tibor T AU - Glant TT FAU - Vermes, Csaba AU - Vermes C FAU - Jacobs, Joshua J AU - Jacobs JJ FAU - Roebuck, Kenneth A AU - Roebuck KA LA - eng GR - AR 45835/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biomed Mater Res A JT - Journal of biomedical materials research. Part A JID - 101234237 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) RN - 0 (Interleukin-8) RN - 0 (NF-kappa B) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 22144-77-0 (Cytochalasin D) RN - D1JT611TNE (Titanium) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Bone Marrow Cells/cytology/*immunology/*physiology MH - Cell Line MH - Chemokine CCL2/immunology MH - Chemokines/*genetics/immunology MH - Cytochalasin D/metabolism MH - Female MH - *Gene Expression Regulation MH - Humans MH - Interleukin-8/immunology MH - Male MH - NF-kappa B/antagonists & inhibitors/metabolism MH - Nucleic Acid Synthesis Inhibitors/metabolism MH - Particle Size MH - Phagocytosis/physiology MH - *Prostheses and Implants MH - Prosthesis Failure MH - Titanium/*immunology MH - Transcriptional Activation EDAT- 2006/01/05 09:00 MHDA- 2006/08/11 09:00 CRDT- 2006/01/05 09:00 PHST- 2006/01/05 09:00 [pubmed] PHST- 2006/08/11 09:00 [medline] PHST- 2006/01/05 09:00 [entrez] AID - 10.1002/jbm.a.30609 [doi] PST - ppublish SO - J Biomed Mater Res A. 2006 Apr;77(1):192-201. doi: 10.1002/jbm.a.30609.