IFN-γ Pretreatment Augments Immune Complex-Induced Matrix Metalloproteinase-1 Expression in U937 Histiocytes

• Published in: Clinical immunology (Orlando, Fla.) Vol. 102; no. 2; pp. 200 - 207
• Main Authors: Anderson, Fran, Game, Bryan A., Atchley, Dan, Xu, Minfu, Lopes-Virella, Maria F., Huang, Yan
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-02-2002; Elsevier
• Subjects: Antigen-Antibody Complex - immunology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; Histiocytes - enzymology; Histiocytes - immunology; Humans; IFN-γ; immune complex; Interferon-gamma - immunology; Interferon-gamma - pharmacology; LDL; Matrix Metalloproteinase 1 - biosynthesis; Matrix Metalloproteinase 1 - immunology; Medical sciences; metalloproteinase; U937 Cells; Up-Regulation - drug effects; Up-Regulation - immunology; IFN-γ; LDL; metalloproteinase; immune complex; EC 3.4.24.7; Histiocyte; Enzyme; Pathogenesis; Cytokine; Cardiovascular disease; Metalloendopeptidases; Vascular disease; Lipoprotein LDL; Peptidases; Atherosclerosis; Established cell line; Hydrolases; Interstitial collagenase; Immune complex; Gamma interferon; Matrilysin
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1006/clim.2001.5161

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-γ (IFN-γ) on IC-induced MMP-1 expression. Our flow cytometry studies showed that IFN-γ upregulated the surface expression of FcγRI, but not FcγRII. Results also showed that pretreatment of the cells with IFN-γ augmented LDL-containing IC (LDL-IC)-induced MMP-1 secretion in a dose- and time-dependent manner. Furthermore, Northern blot analysis revealed that IFN-γ 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-γ or not, suggesting that IFN-γ 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-γ pretreatment augments LDL-IC-induced MMP-1 expression in U937 cells, thus elucidating an immune mechanism potentially involved in plaque destabilization.