The role of titanium in the altered endotoxin-induced nitric oxide synthase expression in alveolar macrophages from titanium-alloy-implanted rats.
We have found that the concentration of titanium (Ti) in the blood of patients with loosened Ti-alloy prostheses is elevated. An increase in the levels of elemental Ti in the blood and lung tissues of rats with an alloyed-Ti implant also has been found. The cellular reaction to elevated elemental Ti in the circulation remains unclear. We further performed experiments to examine the changes of inducible nitric oxide synthase (iNOS) expression in alveolar macrophages from alloyed-Ti-implanted rats. The elevation of nitrite and iNOS expression induced by lipopolysaccharide (LPS) was suppressed. The in vitro effect of a soluble form of Ti was further investigated. Ti (0.01-0.06 mM) inhibited the LPS-induced nitrite production and iNOS expression in alveolar macrophages from normal rats without any cytotoxic effects. LPS induced protein tyrosine phosphorylation, tyrosine-phosphorylation of lyn (a CD14-receptor-associated-tyrosine kinase), and degradation of IkappaB-alpha protein (inhibitor of NF-kappaB) in alveolar macrophages. These events were inhibited by co-incubation with Ti. These results indicate that elemental Ti may impair iNOS expression in alveolar macrophages through the alteration of protein tyrosine phosphorylation and NF-kappaB activation. The inhibitory action of Ti on cellular responses of alveolar macrophages may be anti-inflammatory and thus may depress local defense mechanisms related to microbial killing.
Yang
Rong-Sen
RS
Department of Orthopaedics, College of Medicine, National Taiwan University, Taipei 10043, Taiwan.
Chen
Yi-Hung
YH
Lin-Shiau
Shoei-Yn
SY
Liu
Tang-Kue
TK
Liu
Shing-Hwa
SH
D000497:Alloys; D000818:Animals; D015153:Blotting, Western; D004731:Endotoxins / Q000494:pharmacology*; D005434:Flow Cytometry; D020672:I-kappa B Proteins / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000201:enzymology* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014025:Titanium / Q000097:blood / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000497:Alloys; D004731:Endotoxins; D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; C031462:titanium alloy (TiAl6V4); D000072000:NF-KappaB Inhibitor alpha; D014443:Tyrosine; D014025:Titanium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat