The urokinase plasminogen activator (uPA) is one factor that can activate latent TGF- β.
MMP9, which is involved in the degradation of extracellular matrix components, was reported to mediate N-terminal cleavage of IL-8, to potentiate IL-8 activation of neutrophils [38], and to cleave and activate latent TGF-β2 [39].
These data demonstrate the ability of nanoparticles to target and activate latent HIV in CD4+ cells while minimizing cellular activation of non-targeted cells.
In addition to activation by chemical mediators, recent studies have demonstrated that mechanical forces may activate latent TGF-β via integrin-mediated cellular contractions, or mechanical shearing of blood serum.
Contractile fibroblasts can activate latent TGFβ in the ECM [ 46], suggesting the possibility that simultaneous activation of mechano-receptors and latent, ECM-associated TGFβ may induce contractility in a positive feed-back loop in this fibrosis.
We investigated the ability of SLE patients and control individuals to activate latent TGF-β1 in an in vitro assay that utilizes the physiological activation of latent TGF-β1 that occurs normally during blood clotting.
The light it shines creates chemically potent, oxygen-rich molecules such as hydrogen peroxide which go on to activate latent versions of molecules called transforming growth factor beta 1 (TGF-beta 1).
IGFR also up-regulates Zeb in prostate carcinoma and can activate latent TGF-β1 to induce EMT [30,31].
SAHA can induce hyperacetylation of the HIV promoter-associated nucleosomes to activate latent HIV by suppressing cellular HDAC expression and binding to the HIV promoter [30 32].
Cells that have acquired the ability to activate latent TGFβ induce luciferase expression in the absence but not in the presence of neutralizing antibodies to TGFβ.
Fig. 6 Simultaneous incorporation of suberoylanilide hydroxamic acid (SAHA) and protease inhibitor nelfinavir (Nel) in scFv CD45RO-SAHA/Nel NPs can both activate latent HIV expression and inhibit viral spread.
