Oxidized low-density lipoprotein increases interleukin-8 production in human gingival epithelial cell line Ca9-22.
OBJECTIVE
Recent epidemiological studies have shown a correlation between periodontitis and hyperlipidemia. We have found high levels of oxidized low-density lipoprotein (OxLDL) in the gingival crevicular fluid of dental patients. In the present study, we tried to examine the possible role of OxLDL in periodontal inflammation in vitro.


METHODS
Cells of the human gingival epithelial cell line Ca9-22 were cultured in media containing OxLDL, and the amounts of interleukin-8 (IL-8) and prostaglandin E(2) (PGE(2)) produced were measured using ELISAs.


RESULTS
Production of IL-8 by Ca9-22 cells was significantly increased when the cells were treated with OxLDL, but not with native LDL or acetylated LDL. Production of PGE(2) by Ca9-22 cells was enhanced by co-incubation with OxLDL and interleukin-1 beta (IL-1 beta). Scavenger receptor inhibitors, fucoidan and dextran sulfate, inhibited the OxLDL-induced IL-8 and PGE(2) production in the presence of IL-1 beta. The p(38) MAPK inhibitors SB203580 and SB202190 and the ERK inhibitor PD98059 inhibited the OxLDL-induced IL-8 production. Among oxidized lipids and chemically modified LDL, 7-ketocholesterol enhanced IL-8 production.


CONCLUSIONS
This is the first report to show that OxLDL enhances IL-8 production in epithelial cells.
Suzuki
K
K
Department of Periodontology, Showa University School of Dentistry, Showa University Dental Hospital, Tokyo, Japan.
Sakiyama
Y
Y
Usui
M
M
Obama
T
T
Kato
R
R
Itabe
H
H
Yamamoto
M
M
D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000032:analysis; D002790:Cholesterol 7-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D016264:Dextran Sulfate / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005643:Fucose / Q000494:pharmacology; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000032:analysis / Q000494:pharmacology; D016209:Interleukin-8 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000187:drug effects*; D007653:Ketocholesterols / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D010518:Periodontitis / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors; D013463:Sulfuric Acid Esters / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D053583:Interleukin-1beta; D016209:Interleukin-8; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D011134:Polysaccharides; D011725:Pyridines; D051116:Receptors, Scavenger; D013463:Sulfuric Acid Esters; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D005643:Fucose; D016264:Dextran Sulfate; C007789:fucoidan; D002790:Cholesterol 7-alpha-Hydroxylase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C003001:7-ketocholesterol; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one