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Department of Pharmacology

 
Read more at: Histamine-mediated potentiation of transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 signaling in submucosal neurons in patients with irritable bowel syndrome.

Histamine-mediated potentiation of transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 signaling in submucosal neurons in patients with irritable bowel syndrome.

Previously, we showed histamine-mediated sensitization of transient receptor potential (TRP) vanilloid 1 (TRPV1) in patients with irritable bowel syndrome (IBS). Sensitization of TRP ankyrin 1 (TRPA1) and TRP vanilloid 4 (TRPV4) are also involved in aberrant pain perception in preclinical models of somatic pain. Here, we hypothesize that in parallel with TRPV1, histamine sensitizes TRPA1 and TRPV4, contributing to increased visceral pain in patients with IBS.


Read more at: Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model.


Read more at: Effect of genetic background and postinfectious stress on visceral sensitivity in Citrobacter rodentium-infected mice.

Effect of genetic background and postinfectious stress on visceral sensitivity in Citrobacter rodentium-infected mice.

BACKGROUND: Infectious gastroenteritis is a major risk factor to develop postinfectious irritable bowel syndrome (PI-IBS). It remains unknown why only a subgroup of infected individuals develops PI-IBS. We hypothesize that immunogenetic predisposition is an important risk factor. Hence, we studied the effect of Citrobacter rodentium infection on visceral sensitivity in Th1-predominant C57BL/6 and Th2-predominant Balb/c mice. METHODS: Eight-week-old mice were gavaged with C. rodentium, followed by 1 h of water avoidance stress (WAS) at 5 weeks PI.


Read more at: PR3-anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis.

PR3-anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis.


Read more at: Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis.

Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis.

OBJECTIVE: Psychological factors increase the risk to develop postinfectious IBS (PI-IBS), but the mechanisms involved are unclear. As stress affects the immune system, we investigated the potential interaction between psychological factors, the immune response against infectious gastroenteritis (IGE) and the development of IGE and PI-IBS in a large cohort exposed to contaminated drinking water. DESIGN: 18 620 people exposed to contaminated drinking water (norovirus, Giardia lamblia, Campylobacter jejuni) were invited to participate in a prospective controlled cohort study.


Read more at: Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis.

Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis.

Macrophages are highly heterogeneous tissue-resident immune cells that perform a variety of tissue-supportive functions. The current paradigm dictates that intestinal macrophages are continuously replaced by incoming monocytes that acquire a pro-inflammatory or tissue-protective signature. Here, we identify a self-maintaining population of macrophages that arise from both embryonic precursors and adult bone marrow-derived monocytes and persists throughout adulthood.


Read more at: Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis.

Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis.


Read more at: Prospective study evaluating immune-mediated mechanisms and predisposing factors underlying persistent postinfectious abdominal complaints.

Prospective study evaluating immune-mediated mechanisms and predisposing factors underlying persistent postinfectious abdominal complaints.

BACKGROUND: The role of persistent immune activation in postinfectious irritable bowel syndrome (PI-IBS) remains controversial. Here, we prospectively studied healthy subjects traveling to destinations with a high-risk to develop infectious gastroenteritis (IGE) in order to identify immune-mediated mechanisms and risk factors of PI-IBS. METHODS: One hundred and one travelers were asked to complete questionnaires on psychological profile and gastrointestinal (GI) symptoms before travel, 2 weeks, 6 months and 1 year after travel.


Read more at: Computational modelling of GPCR signalling dynamics

Computational modelling of GPCR signalling dynamics


Read more at: Eukaryotic Initiation factor 4B is a multi-functional RNA binding protein that regulates histone mRNAs

Eukaryotic Initiation factor 4B is a multi-functional RNA binding protein that regulates histone mRNAs

RNA binding proteins drive proliferation and tumorigenesis by regulating the translation and stability of specific subsets of mRNAs. We have investigated the role of eIF4B in this process and identify 10-fold more RNA binding sites for eIF4B in tumour cells from patients with diffuse large B-cell lymphoma compared to control B cells and, using iCLIP, find that eIF4B binds the entire length of mRNA transcripts. eIF4B stimulates the helicase activity of eIF4A thereby promoting the unwinding of RNA structure within the 5’ UTRS of mRNAs.