In vitro studies showed that exposure of HUVECs to VEGF increased the number of adhering monocytes, and PEDF inhibited the VEGF-induced leukostasis in a dose-dependent manner.
K5-NP attenuated vascular endothelial growth factor and intracellular adhesion molecule-1 overexpression and reduced leukostasis and vascular leakage for at least 4 weeks after a single injection in the retina of streptozotocin-induced diabetic rats.
A further study revealed hypoxic trophoblast HMGB1-induced cytotoxicity and leukostasis of HUVEC as well as higher expression of cell adhesion molecules (VCAM-1 and ICAM-1) could be reversed by pretreatment with STS.
In vitro studies showed that exposure of HUVECs to VEGF increased the number of adhering monocytes, and PEDF inhibited the VEGF-induced leukostasis in a dose-dependent manner.
In vivo data demonstrated that the loss of miR-15a/16 in vascular cells led to increased retinal leukostasis and CD45 levels, together with upregulated levels of IL-1β, TNFα, and NF-κB.
Biochemical, genetic and functional studies strongly indicate peroxisome proliferator-activated receptor-γ (PPARγ), a pleiotropic transcription factor, as a primary target in the treatment of diabetic retinopathy.In this issue, Song et al. detail the role of PPARγ in diabetic retinopathy-related disorders, illustrating PPARγ-mediated inhibition of diabetes-induced leukostasis and leakage, and its beneficial role in modulating inflammation, angiogenesis and apoptosis in retinal and endothelial cells.
Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in the pathogenesis of DR by inhibiting diabetes-induced retinal leukostasis and leakage.
Downstream, EC transduce these signals and increase their synthesis and release of chemokines such as CCL8 and CXCL10 that regulate leukostasis and other cellular events related to vascular inflammation in DR. Our results indicate that PPARβ/δ inhibition mitigates these upstream (MC) as well as downstream (EC) inflammatory signaling events elicited by metabolic stimuli and inflammatory cytokines.
Outcome was assessed by analyzing leukostasis using fluorescein isothiocyanate coupled concanavalin A (FITC-ConA) and vessel leakage (bovine serum albumin conjugated with fluorescein isothiocyanate; FITC-BSA)/neovascularization and neurodegeneration by immunohistological approaches (hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL), Brn3a).
On the 15th day post-apoEdp treatment, mouse retinas were harvested to examine (1) blood-retinal-barrier (BRB) permeability by Evans blue dye, inflammatory leukostasis by concanavalin staining of leukocytes and LRP-1 pathway-related protein expression by Western blot analysis and gelatin zymography.
The aim of this study was to determine whether leukostasis is present in the retina, to evaluate the levels of pigment epithelium-derived factor (PEDF) and intracellular adhesion molecule-1 (ICAM-1) levels in the blood of SDT rats, and to examine the effects of PEDF on leukostasis.
A further study revealed hypoxic trophoblast HMGB1-induced cytotoxicity and leukostasis of HUVEC as well as higher expression of cell adhesion molecules (VCAM-1 and ICAM-1) could be reversed by pretreatment with STS.