Publications by authors named "Olaf Welting"
Innervation of the intestinal mucosa by the sympathetic nervous system is well described but the effects of adrenergic receptor stimulation on the intestinal epithelium remain equivocal. We therefore investigated the effect of sympathetic neuronal activation on intestinal cells in mouse models and organoid cultures, to identify the molecular routes involved. Using publicly available single-cell RNA sequencing datasets we show that the α isoform is the most abundant adrenergic receptor in small intestinal epithelial cells.
View Article and Find Full Text PDFBackground: SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn's disease (CD), suggesting a role in inflammation.
Results: We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages.
Article Synopsis
- Vagus nerve stimulation (SpNS) was tested in mice to see if it could reduce inflammation in inflammatory bowel disease (IBD) by targeting the splenic nerve and releasing norepinephrine (NE).
- Mice received stimulation during an induced colitis experiment, showing improved symptoms and lower inflammation markers compared to those with no stimulation.
- The results suggest SpNS may lower immune response activation, indicating potential for clinical application in IBD treatment for humans.
Article Synopsis
- Antimicrobial responses are crucial for gut health, and the study focuses on how miR-511 affects TLR4 responses, leading to increased intestinal inflammation.
- Mice lacking miR-511 showed less severe colitis symptoms and lower inflammatory cytokine levels compared to normal mice when exposed to DSS, indicating a protective role against intestinal inflammation.
- The research also identified Wdfy1 as a target of miR-511, suggesting that diminished WDFY1 levels in miR-511-deficient macrophages contribute to reduced immune responses from TLR3 and TLR4.
Background And Aims: Histone deacetylase inhibitors [HDACi] exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif [ESM] technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 [CES1].
View Article and Find Full Text PDFβ-glucan consumption is known for its beneficial health effects, but the mode of action is unclear. While humans and mice lack the required enzymes to digest β-glucans, certain intestinal microbes can digest β-glucans, triggering gut microbial changes. Curdlan, a particulate β-glucan isolated from , is used as a food additive.
View Article and Find Full Text PDFIn 2020, three articles were published on a protein that can activate the immune system by binding to macrophage-inducible C-type lectin receptor (Mincle). In the articles, the protein was referred to as 'SAP130, a subunit of the histone deacetylase complex.' However, the Mincle ligand the authors aimed to investigate is splicing factor 3b subunit 3 (SF3B3).
View Article and Find Full Text PDFArticle Synopsis
- Recent studies show that SARS-CoV-2 can infect intestinal cells expressing the ACE2 receptor, highlighting the importance of these cells in the virus's entry point.
- The research examined the relationship between nicotinic receptors, inflammation regulation, and ACE2 expression, particularly focusing on the effects of vagus nerve stimulation (VNS) on intestinal epithelial cells.
- Results indicated that while ACE2 and nicotinic receptors are co-expressed in certain intestinal cells, VNS did not influence ACE2 expression, suggesting VNS may not help reduce the risk of SARS-CoV-2 infection in the intestines.
Article Synopsis
- TYK2, a key player in the signaling of cytokines, is critical for the development of inflammatory bowel disease (IBD), and a selective inhibitor (TYK2i) was tested for its effectiveness in treating it in a mouse model of colitis.
- In the study, TYK2i significantly reduced weight loss and disease severity in mice with colitis, while T cells lacking TYK2 activity also showed reduced disease symptoms.
- The findings suggest that targeting TYK2 could be a promising approach for IBD treatment, as it decreased specific immune responses both in mice and human T cells.
Irritable bowel syndrome (IBS) is a heterogenic, functional gastrointestinal disorder of the gut-brain axis characterized by altered bowel habit and abdominal pain. Preclinical and clinical results suggested that, in part of these patients, pain may result from fungal induced release of mast cell derived histamine, subsequent activation of sensory afferent expressed histamine-1 receptors and related sensitization of the nociceptive transient reporter potential channel V1 (TRPV1)-ion channel. TRPV1 gating properties are regulated in lipid rafts.
View Article and Find Full Text PDFAcetylcholine-producing T cells augment innate immune-driven colitis but are redundant in T cell-driven colitis.
Am J Physiol Gastrointest Liver Physiol
November 2019
Article Synopsis
- * Research using mice showed that when ChAT T cells were absent in CD4 T cells, the mice experienced less severe acute colitis but struggled more during the recovery phase compared to control mice.
- * Overall, ChAT T cells can increase inflammation during the early stages of bowel inflammation but are beneficial for the healing process afterward, suggesting a complex role in managing colitis.
Article Synopsis
- The sympathetic nervous system is important for controlling innate immune responses, and its reduction in inflammatory bowel disease affects immune function in the intestines.
- Researchers examined how activation of adrenergic receptors impacts cytokine production in macrophages and studied the effects of sympathetic nerve damage in mice lacking certain immune cells.
- Results showed that nerve damage led to increased inflammation and histological damage in the intestines, indicating that the sympathetic nervous system helps regulate immune cell activity in response to microbial threats.
Background & Aims: Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity.
View Article and Find Full Text PDFBackground: Enhanced colorectal sensitivity (i.e. visceral hypersensitivity) is thought to be a pathophysiological mechanism in irritable bowel syndrome (IBS).
View Article and Find Full Text PDFβ-Glucans have beneficial health effects due to their immune modulatory properties. Oral administration of β-glucans affects tumour growth, microbial infection, sepsis, and wound healing. We hypothesized that pre-treatment with orally delivered soluble and particulate β-glucans could ameliorate the development of aggravate dextran sulfate sodium (DSS) induced intestinal inflammation.
View Article and Find Full Text PDFBackground: Although never evaluated for efficacy, n-3 (ω-3) long-chain polyunsaturated fatty acids (LCPUFAs) are commercially offered as treatment for irritable bowel syndrome (IBS).
Objective: This study was designed to investigate, in a mast cell-dependent model for visceral hypersensitivity, whether this pathophysiologic mechanism can be reversed by dietary LCPUFA treatment via peroxisome proliferator-activated receptor γ (PPARG) activation.
Methods: Maternally separated rats were subjected to hypersensitivity-inducing acute stress at adult age.
Background: The histamine-1 receptor (H1R) antagonist ketotifen increased the threshold of discomfort in hypersensitive IBS patients. The use of peripherally restricted and more selective H1R antagonists may further improve treatment possibilities. We examined the use of fexofenadine and ebastine to reverse post-stress visceral hypersensitivity in maternally separated rats.
View Article and Find Full Text PDFObjectives: Repeated exposure to stress leads to mast cell degranulation, microscopic inflammation, and subsequent visceral hypersensitivity in animal models. To what extent this pathophysiological pathway has a role in patients with the irritable bowel syndrome (IBS) has not been properly investigated. The objective of this study was to assess the relationship between visceral hypersensitivity, microscopic inflammation, and the stress response in IBS.
View Article and Find Full Text PDFBackground: Mast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS.
Methods: 60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment.
Parental care, mast cells and visceral hypersensitivity.
J Pediatr Gastroenterol Nutr
September 2005