Ulinastatin is an acid-resistant protease inhibitor begin in animal urine and appear from the high-molecular-weight forerunner I alpha T1. It inactivates abounding serine proteases, including trypsin, chymotrypsin, kallikrein, plasmin, granulocyte elastase, cathepsin, thrombin, and factors IXa, Xa, XIa, and XlIa. However, although ulinastatin is a protease inhibitor, its action adjoin assorted proteases is almost weak.
Ulinastatin protein has been begin in the brain, liver, kidney, gastrointestinal tract, cartilage, plasma, ovarian follicular fluid, amniotic fluid, and urine. Its mRNA has been detected alone in the liver, kidney, heart, lungs, and pancreas. The attendance of ulinastatin in assertive tissues appears to be due to diffusional uptake and assimilation through corpuscle surfaces. Ulinastatin aswell potentiates bounded anti-proteolytic action on the extracellular cast (ECM) during tissue remodeling, possibly through noncovalent bounden to TSG-6.
Its beard is upregulated by pro-inflammatory cytokines, including IL-6, IL-1beta, and TNF-alpha. These cytokines aswell enhance the amalgam of intracellular I alpha T1 proteins and IL-1beta upregulated ulinastatin. Ulinastatin is active in downregulating or suppressing the assembly of proMMP-1 and proMMP, prostaglandin H2 synthase-2, urokinase, CXC chemokine, pro-inflammatory cytokines, inducible nitric oxide synthase, tissue factor, P-selectin, intercellular adherence molecule-1, phosphorylation of the extracellular signal-regulated protein kinases, and NF-kappaB activation.
Ulinastatin aswell suppresses neutrophil accession and activity. The genes and proteins adapted by ulinastatin are active in the anarchic process. Therefore, ulinastatin is not just a protease inhibitor, but can aswell anticipate deepening and cytokine-dependent signaling pathways. In preclinical and analytic studies, ulinastatin adequate adjoin astute lung injury, affix ischemia/reperfusion injury, renal abortion afterwards cardiopulmonary bypass, astringent bake injury, catchbasin shock, preterm birth, bump invasion, and metastasis. Its anti-metastatic backdrop may appear from the inhibition of cell-bound plasmin activity. Ulinastatin aswell prevents bump progression, partially by inhibiting cathepsin B activity. In particular, ulinastatin is anticipation to arrest CD44 dimerization and abolish the MAP kinase signaling cascade, appropriately preventing ECM degradation, bump corpuscle invasion, and angiogenesis.
Altogether, ulinastatin plays an important role not alone in the aegis of agency abrasion during astringent inflammation, but aswell in the inhibition of bump aggression and metastasis.