IFN-γ 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-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.