In astrocytes, MTDH has been shown to downregulate GLT-1, the gene encoding the major glutamate transporter.
Statins have been shown to downregulate MHC class II and CD40 expression on activated endothelial cells (EC).
Resveratrol has also been shown to downregulate the pro-inflammatory response [14, 58] and to have anti-oxidant properties [11, 57].
Sirolimus has also been shown to downregulate the expression of many genes related to inflammation such as interleukin-8, endothelial monocyte-activating polypeptide II, granulocyte chemotactic protein 2, cyclooxygenase 1 and 2, and inducible nitric oxide synthase [20 23].
Elevated pro-inflammatory cytokines such as tumor necrosis factor (TNF-α) have been shown to downregulate the expression of eNOS (diminishing the dilatory response) in human aortic endothelial cells [34].
As a further complexity, CD40L has been shown to downregulate NALP3-mediated inflammasome activation in macrophages, thereby suppressing the inflammasome-triggered release of inflammatory cytokines [83].
PGRP-SB1 (CG9681) is expressed in gut upon infection [87], and PGRP-LF (CG4437) has been shown to downregulate the Imd pathway [86].
Though not investigated here, CLA has been shown to downregulate COX2 by inhibiting 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate
Moreover, other HDAC inhibitors such as LAQ824, MS-275, FR901228, valproic acid and droxinostat have been shown to downregulate c-FLIP levels and enhance death receptor-induced apoptosis [46] [52].
Temsirolimus is a "rapalog" and rapamycin has been shown to downregulate the EWS-FLI1 fusion protein [26] possibly also lessening IR/IGF1R signaling, and therefore providing an additional pathway by which this molecule might be operative in this patient.
Inflammation has been shown to downregulate NO synthase activity.
