Kallistatin in Sepsis: Protective Actions and Potential Therapeutic Applications

Abstract

Sepsis is a systemic inlammatory response to infection, leading to multiorgan injury and mortality. Kallistatin is an endogenous protein expressed in the liver and tissues relevant to cardiovascular function. Kallistatin levels are markedly reduced in patients with sepsis and liver disease and in lipopolysaccharide (LPS)-induced septic mice. Kallistatin administration atenuates inlammation, multiorgan damage, and lethality in septic mice with LPS treatment, group A streptococcal, or polymicrobial infection. Importantly, kallistatin treatment not only prevents but also reverses organ injury and lethality in septic mice. Kallistatin decreases sepsis-induced inlammatory responses and tissue damage by modulating diferential signaling pathways, including: (1) stimulating endothelial nitric oxide (eNOS) and sirtuin 1 (SIRT) synthesis, and NO formation; (2) increasing suppressor of cytokine signaling-3 (SOCS3) expression; (3) antagonizing tumor necrosis factor-α (TNF-α) and high mobility group box 1 (HMGB1)-mediated oxidative stress and inlammatory gene expression; and (4) displaying bactericidal efects by stimulating superoxide formation. Therefore, kallistatin's multifactorial activities provide efective protection during septic shock in animal models. As kallistatin displays no apparent cytotoxicity, kallistatin therapy may provide a promising approach for the treatment of sepsis in humans.

Spatial-Temporal Characteristics and Influencing Factors of China’s Fishery Industry Development Quality: A Perspective From Development Economics

“…Fiscal expenditure is the main economic behavior of the government, because 'fiscal decentralization structure', 'expenditure bias' and 'local government competition' [46,48,49] are intermediary variables and moderating variables. The possible inhibitory effect on enterprise production efficiency [50], environmental pollution [51], net export [52], urban-rural income gap [53,54] and other variables related to development quality has also been continuously confirmed by relevant studies. In this regard, Zhang has put forward 'effective government theory'.…”