PMID- 12038622
OWN - NLM
STAT- MEDLINE
DCOM- 20020614
LR  - 20131121
IS  - 0736-0266 (Print)
IS  - 0736-0266 (Linking)
VI  - 20
IP  - 3
DP  - 2002 May
TI  - Titanium particles induce the immediate early stress responsive chemokines IL-8 
      and MCP-1 in osteoblasts.
PG  - 490-8
AB  - Exposure of human osteoblasts to ultrafine titanium (Ti) particles has been shown 
      to alter osteoblast gene expression. We previously reported that Ti particles can 
      increase IL-6 release and suppress the gene expression of procollagens alpha1[I] 
      and alpha1[III] in human osteoblasts. In this study, we now demonstrate that Ti 
      particles can rapidly induce the chemotactic cytokines interleukin-8 (IL-8) and 
      monocyte chemoattractant protein-1 (MCP-1), two immediate early stress responsive 
      chemokines important for the activation and chemotaxis of neutrophils and 
      macrophages, respectively. In MG-63 osteosarcoma cells and bone marrow derived 
      primary osteoblasts Ti particles selectively increased the steady state levels of 
      IL-8 and MCP-1 mRNA in a time and concentration dependent manner. The increased 
      chemokine mRNA correlated with increased secretion of IL-8 and MCP-1 protein. 
      Actinomycin D, a potent RNA polymerase II inhibitor, blocked the Ti particle 
      induction of IL-8 and MCP-1 mRNA expression, whereas cycloheximide, which 
      inhibits protein synthesis, failed to inhibit chemokine gene expression 
      suggesting Ti particles directly target activation of chemokine gene 
      transcription. Consistent with a transcriptional mechanism not involving new 
      protein synthesis, we demonstrate that Ti particles induce the binding of the p65 
      and p50 subunits of the latent transcription factor NF-kappaB to the IL-8 gene 
      promoter. Taken together, these data demonstrate that Ti particles can activate 
      transcription of the stress responsive chemokine genes IL-8 and MCP-1 in human 
      osteoblasts.
FAU - Fritz, Elizabeth A
AU  - Fritz EA
AD  - Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical 
      Center, Rush University, Chicago, IL 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, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Orthop Res
JT  - Journal of orthopaedic research : official publication of the Orthopaedic 
      Research Society
JID - 8404726
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 9007-49-2 (DNA)
RN  - D1JT611TNE (Titanium)
SB  - IM
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - DNA/metabolism
MH  - Humans
MH  - Interleukin-8/*biosynthesis/genetics
MH  - NF-kappa B/metabolism
MH  - Osteoblasts/*metabolism
MH  - Promoter Regions, Genetic/physiology
MH  - RNA, Messenger/metabolism
MH  - Stress, Physiological/*metabolism
MH  - Titanium/*pharmacology
MH  - Transcription, Genetic/drug effects
MH  - Tumor Cells, Cultured
EDAT- 2002/06/01 10:00
MHDA- 2002/06/18 10:01
CRDT- 2002/06/01 10:00
PHST- 2002/06/01 10:00 [pubmed]
PHST- 2002/06/18 10:01 [medline]
PHST- 2002/06/01 10:00 [entrez]
AID - 10.1016/S0736-0266(01)00154-1 [doi]
PST - ppublish
SO  - J Orthop Res. 2002 May;20(3):490-8. doi: 10.1016/S0736-0266(01)00154-1.