IFN-gamma pretreatment augments immune complex-induced matrix metalloproteinase-1 expression in U937 histiocytes.
We reported recently that immune complexes (ICs) induced matrix metalloproteinase-1 (MMP-1) expression in U937 histiocytes. The present study was undertaken to determine the effect of pretreatment of U937 cells with interferon-gamma (IFN-gamma) on IC-induced MMP-1 expression. Our flow cytometry studies showed that IFN-gamma upregulated the surface expression of FcgammaRI, but not FcgammaRII. Results also showed that pretreatment of the cells with IFN-gamma augmented LDL-containing IC (LDL-IC)-induced MMP-1 secretion in a dose- and time-dependent manner. Furthermore, Northern blot analysis revealed that IFN-gamma pretreatment led to a marked increase in MMP-1 mRNA. Finally, we demonstrated that PD98059 was able to block LDL-IC-induced MMP-1 secretion, regardless of whether the cells were pretreated with IFN-gamma or not, suggesting that IFN-gamma pretreatment did not alter the essential role of the ERK signaling pathway in LDL-IC-induced MMP-1 expression. In conclusion, the present study has demonstrated that IFN-gamma pretreatment augments LDL-IC-induced MMP-1 expression in U937 cells, thus elucidating an immune mechanism potentially involved in plaque destabilization.
Anderson
Fran
F
Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina 29401, USA.
Game
Bryan A
BA
Atchley
Dan
D
Xu
Minfu
M
Lopes-Virella
Maria F
MF
Huang
Yan
Y
D000936:Antigen-Antibody Complex / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006644:Histiocytes / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000276:immunology; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000936:Antigen-Antibody Complex; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007371:Interferon-gamma; D020781:Matrix Metalloproteinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one