Galit Shahaf

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The rationale of α1-antitrypsin (AAT) augmentation therapy to treat progressive emphysema in AAT-deficient patients is based on inhibition of neutrophil elastase; however, the benefit of this treatment remains unclear. Here we show that clinical grade AAT (with elastase inhibitory activity) and a recombinant form of AAT (rAAT) without anti-elastase activity(More)
Antiinflammatory clinical-grade, plasma-derived human α-1 antitrypsin (hAAT) protects islets from allorejection as well as from autoimmune destruction. hAAT also interferes with disease progression in experimental autoimmune encephalomyelitis (EAE) and in collagen-induced arthritis (CIA) mouse models. hAAT increases IL-1 receptor antagonist expression in(More)
Tolerogenic IL-10-positive CCR7-positive dendritic cells (DC) promote T regulatory (Treg) cell differentiation upon CCR7-dependent migration to draining lymph nodes (DLN). Indeed, in human DC deficiencies, Treg levels are low. α-1 antitrypsin (AAT) has been shown to reduce inflammatory markers, promote a semimature LPS-induced DC phenotype, facilitate Treg(More)
Pancreatic islets are a highly vascularized entity, and their transplantation into diabetic individuals requires optimal revascularization. In addition, β-cells in islets are extremely sensitive to inflammation. α-1-Antitrypsin (AAT), a circulating serine-protease inhibitor that is available for clinical use as an affinity-purified human product, has been(More)
BACKGROUND Severe bacterial infection can cause sepsis, multiple organ dysfunction syndrome (MODS), and death. Human α1-antitrypsin (hAAT) is an antiinflammatory, immune-modulating, and tissue-protective circulating serine-protease inhibitor, with levels that increase during acute-phase responses. It is currently being evaluated as a therapeutic agent for(More)
The PI3K-AKT pathway is frequently activated in human cancers, including breast cancer, and its activation appears to be critical for tumor maintenance. Some malignant cells are dependent on activated AKT for their survival; tumors exhibiting elevated AKT activity show sensitivity to its inhibition, providing an Achilles heel for their treatment. Here we(More)
Protein kinase C (PKC) represents a family of serin/threonine kinases, playing a central role in the regulation of cell growth, differentiation and transformation. These enzymes differ in their primary structure, biochemical properties, tissue distribution and subcellular localization. The specific cellular functions of PKC isoforms are largely controlled(More)
Although islet transplantation for individuals with type 1 diabetes has been shown to yield superior blood glucose control, it remains inadequate for long-term control. This is partly due to islet injuries and stresses that can lead to beta cell loss. Inhibition of excess IL-1β activity might minimize islet injuries, thus preserving function. The IL-1(More)
The extracellular form of the abundant heat-shock protein, gp96, is involved in human autoimmune pathologies. In patients with type 1 diabetes, circulating gp96 is found to be elevated, and is bound to the acute-phase protein, α1-antitrypsin (AAT). The two molecules also engage intracellularly during the physiological folding of AAT. AAT therapy promotes(More)
Alpha-1-antitrypsin (AAT) is the primary circulating serine protease inhibitor, and is known to exert potent anti-inflammatory effects and to inhibit the progression of several autoimmune diseases. In this study, transgenic mice that over-express surfactant-driven human (h)AAT on the C57BL/6 background were evaluated for resistance to MOG-35-55(More)