Figure 6. Signaling pathways in macrophage plasminogen activation.

A) Macrophage cultures were stimulated or not with IFNγ in the presence or absence of antibodies to the IFNγ receptor (R1, R2) and tPA expression by RT-PCR and inset) p-STAT signaling monitored by Western blot. IFNγ significantly enhanced tPA relative to control, unstimulated macrophages (A, *p<0.001). As evident, phosphorylations of STAT1 and particularly, STAT3 and STAT5 were inhibited in the presence of antibody to R2 (inset), which resulted in significantly blunted expression of tPA relative to IFNγ-only treated macrophages. *p<0.001; **p<0.01. B. Macrophage cultures were stimulated or not with IFNα in the presence or absence of antibodies to IFNAR (CD118) and tPA levels monitored by RT-PCR (B) and p-STAT signaling monitored by Western blot (inset). Phosphorylations of STAT1, STAT3 and STAT5 were all inhibited in the presence of the antibody, which resulted in significant blockage of tPA expression relative to IFNα. *p<0.01. C,D) Using a Jak1/2 inhibitor, both IFNα and IFNγ signaling pathways were interrupted with near loss of STAT phosphorylation as determined by Western blot using STAT6 protein as loading control. No inhibition was seen on constitutive pNFκB. E) In the presence of the Jak inhibitor, IFNγ-induced tPA expression was significantly inhibited. *p=0.01 comparing IFNγ only with IFNγ + Jak Inh.