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Synergistic induction of cyclooxygenase-II by bacterial lipopolysaccharide in combination with particles of medical device materials in a murine macrophage cell line J774A.1

 Dong Hee Lee  ;  Jong-Chul Park  ;  Hwal Suh 
 Journal of Biomedical Materials Research, Vol.55(4) : 547-553, 2001 
Journal Title
 Journal of Biomedical Materials Research 
Issue Date
Animals ; Biocompatible Materials/adverse effects ; Biocompatible Materials/pharmacology* ; Biological Assay ; Cell Line ; Cyclooxygenase 2 ; Drug Synergism ; Enzyme Induction/drug effects ; Inflammation/etiology ; Isoenzymes/analysis ; Isoenzymes/biosynthesis* ; Lipopolysaccharides/pharmacology* ; Macrophage Activation/drug effects ; Macrophages/drug effects ; Macrophages/enzymology* ; Macrophages/immunology ; Mice ; Prostaglandin-Endoperoxide Synthases/analysis ; Prostaglandin-Endoperoxide Synthases/biosynthesis*
biomaterials ; cyclooxygenase‐II ; synergistic ; inflammation ; macrophage ; J774A.1 ; arachidonic acid ; prostaglandin
Corrosion and wear of implanted medical devices may produce particulate debris, leading to acute and chronic inflammatory responses in the host. In the presence of biomaterial wear particles, host monocytes/macrophages are activated to synthesize or secrete mediators of inflammation. In order to understand the mechanisms underlying the host response to particulates and device-associated infections, we have focused on the effects of medical device particles on macrophage function, because these cells play a pivotal role in the body's response to foreign bodies and their interaction with other cellular components of the immune system. In order to evaluate the effects of particles of medical device materials on functional activities of macrophages, we developed a cyclooxygenase-II (COX-II) assay system using J774A.1 macrophages. Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible COX-II is induced by some cytokines, mitogens, and endotoxin, presumably in pathological conditions such as inflammation. We have evaluated the inductive effects of implant materials, i.e., particles of polymethylmethacrylate (PMMA), hydroxyapatite (HA), titanium oxide, and silica, on the activity of COX-II using thin layer chromatography of prostaglandin D2 (PGD2) formed from [1-14C]-labeled arachidonic acid (AA). Also, we have assessed the synergistic effects of these particles on lipopolysaccharide (LPS)-mediated macrophage activation. Addition of LPS to these particles increased PGD2 production several-fold greater than the addition of any inducer alone. Our results indicated that device-associated infections could enhance inflammatory responses to the wear particles in subjects with medical implants or in whom particulate biomaterials are used for clinical purposes. The use of this model COX-II assay system may lead to the identification of inflammatory potentials for implant materials more specifically than present in vivo assays.
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1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
Yonsei Authors
Park, Jong Chul(박종철) ORCID logo https://orcid.org/0000-0003-0083-5991
Suh, Hwal(서활)
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