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In the skin of normal and atopic individuals, the expression of E‐selecting (ELAM‐l), L‐selectin (LECAM‐l), P‐selection (CD62), CD31 (PECAM), vascular cell adhesion molecule‐1 (VCAM‐l), intercellular adhesion molecule‐1 (ICAM‐l), and cutaneous lymphocyte antigen (CLA) were compared by immunostaining of skin biopsies which were taken from normal individuals (n= 17), the healthy‐appearing skin of patients with atopic dermatitis (n = lo), and their acute (n = 5) and chronic (n = 6) skin lesions. In contrast to ELAM‐1, the expression of VCAM‐1 and ICAM‐1 was found to be significantly increased in non lesional atopic skin in comparison to the skin of normal individuals. Moreover, in contrast to normal skin of healthy individuals, nonlesional atopic skin showed a further increase of VCAM‐1, ICAM‐1, and ELAM‐1 when cultured with medium alone. This suggests that certain adhesion molecules are constitutively upregulated in healthy‐appearing skin of patients with atopic dermatitis. In addition, atopic skin appears to respond to nonspecific stimuli (such as culture with medium alone) with upregulation of VCAM‐1, ICAM‐1, and ELAM‐1. It is suggested that the observed upregulation of adhesion molecules is mediated by the release of cytokines such as interleukin‐4 from cells which reside in atopic skin. The question of whether the inherent up regulation of adhesion molecules in atopic skin contributes to the development of Th2 cells, which have been found to predominate in atopic inflammation, has to be further investigated.

The hepatic phosphatidylcholine (PC) transporter ATP-binding cassette (ABC) B4 flops PC from hepatocytes into bile, and its dysfunction causes chronic cholestasis and fibrosis. Because a nuclear receptor-dependent PC pathway has been determined to exert antidiabetic effects, we now analyzed the role of ABCB4 in glucose metabolism. We bred congenic Abcb4-knockout (Abcb4(-/-)) mice on the fibrosis-susceptible BALB/cJ background. Knockout mice and wild-type controls were phenotyped by measuring plasma glucose concentrations, intraperitoneal glucose tolerance, hepatic RNA expression profiles, and liver histology. In addition, 4 procholestatic ABCB4 gene variants were correlated with blood glucose levels in 682 individuals from 2 independent European cohorts. Systemic glucose levels differ significantly between Abcb4(-/-) mice and wild-type controls, and knockout mice display improved glucose tolerance with significantly lower area under the curve values on intraperitoneal glucose challenge. Of note, hepatic expression of the antidiabetic nuclear receptor 5A2 (LRH-1) is induced consistently in Abcb4(-/-) mice, and its specific rare PC ligands are detected in liver by mass spectrometry imaging. In humans, serum glucose levels are associated significantly with the common ABCB4 variant c.711A>T. In summary, ABCB4 might play a critical role in glucose homeostasis in mice and humans. We speculate that the effects could be mediated via LRH-1-dependent PC pathways.

Changes in CD446 expression level do not predict tumour spread or patient survival in colorectal cancer.

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