FIG. 5.
Regulation of MMP-2 and -9 levels in human U937 monocytoid cells (A) and primary feline macrophages (B, C) by the STAT/JAK signaling pathway. Uninfected U937 (A) or feline macrophage (B) cultures were incubated in the presence (+) or absence (−) of IFN-α (100 IU/ml), RANTES (50 ng/ml), or fludarabine (FLUD; 50 μM) for 24 h. IFN-α and RANTES significantly increased MMP-2 and -9 expression in both human (A) and feline (B) cultures compared to those in untreated controls. Fludarabine partially attenuated this effect. (C) Conditioned media from feline macrophages, infected with V1CSF, Petaluma (Pet), or chimeric (FIV-Ch) FIV strains at titers of 102 TCID50/106 cells (+) or 103.5 TCID50/106 cells (++), exhibited increased MMP-2 and -9 levels. MMP levels were dependent on the viral strain, with V1CSF and FIV-Ch showing higher levels than those in Petaluma or uninfected controls at day 3 postinfection. Parallel cultures infected with Pet or FIV-Ch viruses, incubated with fludarabine for 24 h, disclosed significant reductions in MMP levels, especially MMP-2. Data are expressed as fold increases over uninfected controls and represent the mean ± standard deviation of three experiments. Significant differences relative to control cultures are indicated (Tukey-Kramer test; ∗, P < 0.05; ∗∗, P < 0.01).