Ulinastatin is a glycoprotein that is isolated from healthy human urine or synthetically produced and has molecular weight of 25 - 40kDa.
[3] Ulinastatin is an acid-resistant protease inhibitor found in human urine and released from the high-molecular-weight precursor I alpha T1.
It inactivates many serine proteases, including trypsin, chymotrypsin, kallikrein, plasmin, granulocyte elastase, cathepsin, thrombin, and factors IXa, Xa, XIa, and XlIa.
Ulinastatin also potentiates local anti-proteolytic activity on the extracellular matrix (ECM) during tissue remodeling, possibly through noncovalent binding to TSG-6.
Ulinastatin is implicated in downregulating or suppressing the production of proMMP-1 and proMMP, prostaglandin H2 synthase-2, urokinase, CXC chemokine, pro-inflammatory cytokines, inducible nitric oxide synthase, tissue factor, P-selectin, intercellular adhesion molecule-1, phosphorylation of the extracellular signal-regulated protein kinases, and NF-kappaB activation.
In particular, ulinastatin is thought to inhibit CD44 dimerization and suppress the MAP kinase signaling cascade, thus preventing ECM degradation, tumor cell invasion, and angiogenesis.
Altogether, ulinastatin plays an important role not only in the protection of organ injury during severe inflammation, but also in the inhibition of tumor invasion and metastasis.