Urotensin II: an inflammatory cytokine.

Urotensin II (UII) is a polypeptide molecule with neurohormone-like activity. It has been confirmed that UII is widely distributed in numerous organs of different animal species from fish to mammals, including humans. The UII receptor is orphan G-protein coupled receptor 14, also known as UT. The tissue distribution of UII and UT is highly consistent, and their expression may be regulated by autocrine and paracrine mechanisms. In the body, UII has many physiological and pathophysiological activities, such as vasoconstrictor and vasodilatory actions, cell proliferation, pro-fibrosis, neuroendocrine activity, insulin resistance, and carcinogenic and inflammatory effects, which have been recognized only in recent years. In fact, UII is involved in the process of inflammatory injury and plays a key role in the onset and development of inflammatory diseases. In this paper, we will review the roles UII plays in inflammatory diseases.

A role of cell apoptosis in lipopolysaccharide (LPS)-induced nonlethal liver injury in D-galactosamine (D-GalN)-sensitized rats.

Lipopolysaccharide (LPS) is implicated in the pathology of acute liver injury and can induce lethal liver failure when simultaneously administered with D-galactosamine (D-GalN). At the present time, nonlethal liver failure, the liver injury of clinical implication, is incompletely understood following challenge by low-dose LPS/D-GalN. We report here our investigation of the effects of liver injury following a nonlethal dose LPS/D-GalN and the role of apoptosis in this disorder. Blood biochemistry indexes, including those of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL), had risen by 6 h post-LPS/D-GalN injection, reached a peak at 24 h and sustained high levels at 48 h. An abnormal liver appearance was found at 24 and 48 h post-injection. Histopathological changes of hepatic injuries accompanied by hepatocellular death, inflammatory infiltration and hemorrhage began to appear at 6 h and were markedly aggravated at 24 and 48 h. Cell apoptosis was significantly induced by the nonlethal dose LPS/D-GalN challenge, and the apoptotic indexes (AIs) in 24 h- and 48 h-treated rats were approximately 70%, as estimated by the terminal transferase dUTP nick end labeling (TUNEL) assay. The mRNA levels of the inflammatory cytokine IL-1beta rose markedly at 6 h and maintained high levels at 24 and 48 h; however, TNF-alpha levels were normal in the liver tissues of 6-, 24- and 48-h-treated rats. mRNA expression of the damage gene nitric oxide synthase (NOS) was also induced early by the LPS/D-GalN challenge, reaching a peak at 6 h, then gradually decreasing in a stepwise manner; conversely, high expression levels of the apoptosis-inducing gene p53 mRNA were not found in the early post-injection period (6 h) but emerged in the crest-time of liver apoptosis (24 h) and were maintained at this level until the late stage (48 h). We also observed that in 24 h-treated rats, caspase-3, -8, -9 and -12 were markedly activated by LPS/D-GalN challenge. These results suggest that a challenge with low-dose LPS in conjunction with D-GalN can induce nonlethal but marked liver failure, the main morphological feature of which is hepatic apoptosis, which may be associated with a high expression of inducible (i)NOS (early post-injection period) and p53 genes (in the mid and late stages) and at least three apoptosis pathways participate in the pathogenesis.