Non-canonical STAT3 function reduces REDD1 transcription.

The transcription factor STAT3 is a potent activator of transcription, but evidence exists that STAT3 can also repress gene expression. However, little is known about the molecular mechanisms involved in STAT3-dependent gene repression. Notably, STAT3 reduces the expression of the stress-induced mTOR inhibitor REDD1 by reducing REDD1 mRNA transcription.

Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling.

Cellular communication via intracellular signalling pathways is crucial. Expression and activation of signalling proteins is heterogenous between isogenic cells of the same cell-type. However, mechanisms evolved to enable sufficient communication and to ensure cellular functions.

Interleukin-6 influences stress-signalling by reducing the expression of the mTOR-inhibitor REDD1 in a STAT3-dependent manner.

Interleukin 6 (IL-6) is a pleiotropic cytokine and a strong activator of Mammalian Target of Rapamycin (mTOR). In contrast, mTOR activity is negatively regulated by Regulated in Development and DNA Damage Responses 1 (REDD1). Expression of REDD1 is induced by cellular stressors such as glucocorticoids and DNA damaging agents.

Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction.

Background: The hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of tissues, including epithelial cells, on binding to the receptor tyrosine kinase c-Met. Abnormal c-Met signalling contributes to tumour genesis, in particular to the development of invasive and metastatic phenotypes. The human microbial pathogen Helicobacter pylori can induce chronic gastritis, peptic ulceration and more rarely, gastric adenocarcinoma.

The Fusarium toxin deoxynivalenol disrupts phenotype and function of monocyte-derived dendritic cells in vivo and in vitro.

The trichothecene mycotoxin deoxynivalenol (DON) causes systemic immuno-suppression in pigs and possibly also in humans after chronic dietary exposure. Since the outcome of every immune response is largely controlled by dendritic cells (DC), we hypothesised that a direct influence of DON on DC function might play a role in mediating DON immunotoxicity. To test this hypothesis, a 2x2 factorial design study was performed.

Cholera toxin promotes the generation of semi-mature porcine monocyte-derived dendritic cells that are unable to stimulate T cells.

Cholera toxin (Ctx) is a powerful mucosal adjuvant with potential applications for oral vaccination of swine. Dendritic cells (DC) play a key role in the decision between immunity and tolerance, and are likely target cells for mediating Ctx functions in vivo. Therefore, we examined the capacity of Ctx to enhance stimulatory activity of porcine monocyte-derived DC (MoDC).

Receptor endocytosis counteracts the development of opioid tolerance.

In contrast to endogenous opioids, the highly addictive drug morphine activates the mu-opioid receptor without causing its rapid endocytosis. It has recently been reported that coapplication of low concentrations of [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) facilitates the ability of morphine to stimulate mu-opioid receptor endocytosis and prevents the development of morphine tolerance in rats. To investigate the clinical relevance of this finding for analgesic therapy, the endocytotic efficacies of a series of clinically used opioids were determined, and the effect of a combination of these drugs with morphine on the mu-opioid receptor endocytosis in receptor-expressing human embryonic kidney (HEK) 293 cells was quantified.