Although the anti-inflammatory effect of interleukin-1 (IL-1) receptor antagonist (IL-1Ra) has been described, the contribution of this cytokine to cholesterol metabolism remains unclear. Our aim was to ascertain whether deficiency of IL-1Ra deteriorates cholesterol metabolism upon consumption of an atherogenic diet. IL-1Ra-deficient mice (IL-1Ra ؊/؊ ) showed severe fatty liver and portal fibrosis containing many inflammatory cells following 20 weeks of an atherogenic diet when compared with wild type (WT) mice. Expectedly, the levels of total cholesterol in IL-1Ra ؊/؊ mice were significantly increased, and the start of lipid accumulation in liver was observed earlier when compared with WT mice. Realtime PCR analysis revealed that IL-1Ra ؊/؊ mice failed to induce mRNA expression of cholesterol 7␣-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, with concurrent up-regulation of small heterodimer partner 1 mRNA expression. Indeed, IL-1Ra ؊/؊ mice showed markedly decreased bile acid excretion, which is elevated in WT mice to maintain cholesterol level under atherogenic diet feeding. Therefore, we conclude that the lack of IL-1Ra deteriorates cholesterol homeostasis under atherogenic diet-induced inflammation.

No abstract

To identify new target marker genes in renal cell carcinoma (RCC), we compared the gene expression profiles of clear cell RCC (cc-RCC) and normal kidney tissue using serial analysis of gene expression. Our results revealed that the transforming growth factor ß induced 68 kDa protein (TGF-ßI: ß ig-h3 (BIGH3), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor ß1 (TGF-ß1) genes are upregulated in cc-RCC. To further assess the role of BIGH3 in RCC, we investigated the mRNA expression levels of BIGH3, TGFß1, PAI-1 and also of TGF-ß1 related genes in 53 RCC and 30 normal kidney tissues by quantitative real-time RT-PCR (QRT-PCR). We further determined the BIGH3 protein levels in 52 cc-RCC paraffin-embedded tissue samples by immunohistochemistry. BIGH3 mRNA was found to be highly overexpressed in cc-RCC compared with normal tissues with an average ratio of 27. The mRNA levels of TGF-ß1 and PAI-1 were also detected at significantly elevated levels in these cancers. Immunohistochemical analysis of BIGH3 also revealed strong staining in the majority of the cc-RCC samples. In addition, the up-regulation of BIGH3 and PAI-1 was found to correlate with the clinicopathological parameters associated with a poorer patient outcome, whereas TGF-ß1 expression was determined to be unrelated to cancer progression. Strong BIGH3 staining thus tended to be associated with a poor prognosis. BIGH3 was also induced in some RCC cell lines by TGF-ß1 stimulation and this correlated well with PAI-1 upregulation, suggesting that these enhancements are regulated by a similar mechanism in these tumors.

A case of primary malignant fibrous histiocytoma of the bladder is presented. This tumor involving the bladder is rare and the unusual histological features in the present case caused significant delay in accurate diagnosis. Since early diagnosis and aggressive surgical resection are essential to the effective treatment of this neoplasm, physicians should continually bear in mind the possibility of this malignant tumor whenever the pathological diagnosis is inconclusive.

It is suggested that examination of Skp2 expression might be clinically useful for prognostication in patients with pancreatic carcinoma and that Skp2 protein might be a novel therapeutic molecular target.