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Metabolites Sep 2022Within the gastrointestinal tract, histamine is present at relatively high concentrations, especially during inflammatory processes. Histamine is a biogenic amine with... (Review)
Review
Within the gastrointestinal tract, histamine is present at relatively high concentrations, especially during inflammatory processes. Histamine is a biogenic amine with numerous effects on many cell types, mediated by the activation of its four different histamine receptors (H1-H4Rs). It is produced and released by immune cells as mast cells and basophils. Some cells such as dendritic cells or T cells can express histidine decarboxylase, an enzyme for histamine synthesis after stimulation. The same can be done by the human gut microbiota. The production of histamine by bacteria in the human gut influence the immune response, although the major source of histamine is food. The large spectrum of histamine effects on a number of cellular processes results in various gastrointestinal disorders including food allergy, histamine intolerance, irritable bowel syndrome, and inflammatory bowel disease, among others. In this review, the protective or pathogenic effects of histamine on various gut disorders are discussed.
PubMed: 36295796
DOI: 10.3390/metabo12100895 -
Biomedical Journal Apr 2022Gilles de la Tourette syndrome (TS) is a common, childhood-onset psychiatric disorder characterized by persistent motor and vocal tics. It is a heterogeneous disorder in... (Review)
Review
Gilles de la Tourette syndrome (TS) is a common, childhood-onset psychiatric disorder characterized by persistent motor and vocal tics. It is a heterogeneous disorder in which the phenotypic expression may be affected by environmental factors, such as immune responses. Furthermore, several studies have shown that genetic factors play a vital role in the etiology of TS, as well as its comorbidity with other disorders, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, and autism spectrum disorder. TS has a complex inheritance pattern and, according to various genetic studies, several genes and loci have been correlated with TS. Genome-wide linkage studies have identified Slit and Trk-like 1 (SLITRK1) and histidine decarboxylase (HDC) genes, and candidate gene association studies have extensively investigated the dopamine and serotonin system genes, but there have been no consistent results. Moreover, genome-wide association studies have implicated several genetic loci; however, larger study cohorts are needed to confirm this. Copy number variations, which are polymorphisms in the number of gene copies due to chromosomal deletions or duplications, are considered another significant source of mutations in TS. In the last decade, whole genome/exome sequencing has identified several novel genetic mutations in patients with TS. In conclusion, more studies are needed to reveal the exact mechanisms of underlying TS, which may help to provide more information on the prognosis and therapeutic plans for TS.
Topics: Autism Spectrum Disorder; Child; DNA Copy Number Variations; Genetic Linkage; Genome-Wide Association Study; Humans; Tourette Syndrome
PubMed: 35042017
DOI: 10.1016/j.bj.2022.01.008 -
Cell Stem Cell Nov 2022The communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of...
The communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of glioblastoma multiforme (GBM). However, the mechanisms by which GSCs proactively drive interactions with microenvironment is not well understood. In this study, we interrogated metabolites that are preferentially secreted from GSCs and found that GSCs produce and secrete histamine to shape a pro-angiogenic tumor microenvironment. This histamine-producing ability is attributed to H3K4me3 modification-activated histidine decarboxylase (HDC) transcription via MYC. Notably, HDC is highly expressed in GBM, which is associated with poor survival of these patients. GSC-secreted histamine activates endothelial cells by triggering a histamine H1 receptor (HR)-Ca-NF-κB axis, thereby promoting angiogenesis and GBM progression. Importantly, pharmacological blockage of HR using antihistamines impedes the growth of GBM xenografts in mice. Our findings establish that GSC-specific metabolite secretion remodels the tumor microenvironment and highlight histamine targeting as a potential strategy for GBM therapy.
Topics: Humans; Mice; Animals; Glioblastoma; Histamine; Tumor Microenvironment; Brain Neoplasms; Endothelial Cells; Neoplastic Stem Cells; Cell Line, Tumor
PubMed: 36265493
DOI: 10.1016/j.stem.2022.09.009 -
Genes To Cells : Devoted To Molecular &... Jul 2020Histamine is a bioactive monoamine that is synthesized by the enzymatic activity of histidine decarboxylase (HDC) in basophils, mast cells, gastric enterochromaffin-like... (Review)
Review
Histamine is a bioactive monoamine that is synthesized by the enzymatic activity of histidine decarboxylase (HDC) in basophils, mast cells, gastric enterochromaffin-like (ECL) cells and histaminergic neuronal cells. Upon a series of cellular stimuli, these cells release stored histamine, which elicits allergies, inflammation, and gastric acid secretion and regulates neuronal activity. Recent studies have shown that certain other types of myeloid lineage cells also produce histamine with HDC induction under various pathogenic stimuli. Histamine has been shown to play a series of pathophysiological roles by modulating immune and inflammatory responses in a number of disease conditions, whereas the mechanistic aspects underlying induced HDC expression remain elusive. In the present review, we summarize the current understanding of the regulatory mechanism of Hdc gene expression and the roles played by histamine in physiological contexts as well as pathogenic processes. We also introduce a newly developed histaminergic cell-monitoring transgenic mouse line (Hdc-BAC-GFP) that serves as a valuable experimental tool to identify the source of histamine and dissect upstream regulatory signals.
Topics: Animals; Chromosomes, Artificial, Bacterial; Gene Expression Regulation, Enzymologic; Histamine; Histidine Decarboxylase; Histones; Methylation; Mice; Mice, Transgenic; Myeloid Cells; Receptors, Histamine; Sepsis
PubMed: 32394600
DOI: 10.1111/gtc.12774 -
International Journal of Molecular... Jan 2019Histamine is a well-known mediator of inflammation that is released from mast cells and basophils. To date, many studies using histamine receptor antagonists have shown... (Review)
Review
Histamine is a well-known mediator of inflammation that is released from mast cells and basophils. To date, many studies using histamine receptor antagonists have shown that histamine acts through four types of receptors: H1, H2, H3, and H4. Thus, histamine plays more roles in various diseases than had been predicted. However, our knowledge about histamine-producing cells and the molecular mechanisms underlying histamine production at inflammatory sites is still incomplete. The histamine producing enzyme, histidine decarboxylase (HDC), is commonly induced at inflammatory sites during the late and chronic phases of both allergic and non-allergic inflammation. Thus, histamine levels in tissues are maintained at effective concentrations for hours, enabling the regulation of various functions through the production of cytokines/chemokines/growth factors. Understanding the regulation of histamine production will allow the development of a new strategy of using histamine antagonists to treat inflammatory diseases.
Topics: Animals; Histamine; Histidine Decarboxylase; Humans; Inflammation; Mast Cells
PubMed: 30654600
DOI: 10.3390/ijms20020376 -
Frontiers in Immunology 2018Histamine is a critical mediator of IgE/mast cell-mediated anaphylaxis, a neurotransmitter and a regulator of gastric acid secretion. Histamine is a monoamine... (Review)
Review
Histamine is a critical mediator of IgE/mast cell-mediated anaphylaxis, a neurotransmitter and a regulator of gastric acid secretion. Histamine is a monoamine synthesized from the amino acid histidine through a reaction catalyzed by the enzyme histidine decarboxylase (HDC), which removes carboxyl group from histidine. Despite the importance of histamine, transcriptional regulation of gene expression in mammals is still poorly understood. In this review, we focus on discussing advances in the understanding of molecular regulation of mammalian histamine synthesis.
PubMed: 29973935
DOI: 10.3389/fimmu.2018.01392 -
Brain and Behavior Mar 2022Tourette syndrome (TS) is caused by complex genetic and environmental factors and is characterized by tics. Histidine decarboxylase (HDC) mutation is a rare genetic... (Review)
Review
Tourette syndrome (TS) is caused by complex genetic and environmental factors and is characterized by tics. Histidine decarboxylase (HDC) mutation is a rare genetic cause with high penetrance in patients with TS. HDC-knockout (KO) mice have similar behavioral and neurochemical abnormalities as patients with TS. Therefore, HDC-KO mice are considered a valuable TS pathophysiological model as it reveals the underlying pathological mechanisms that cannot be obtained from patients with TS, thus advancing the development of treatment strategies for TS and other tic disorders. This review summarizes some of the recent research hotspots and progress in HDC-KO mice, aiming to deepen our understanding of brain mechanisms relevant to TS. Furthermore, we encapsulate the possible brain nerve cell changes in HDC-KO mice and their potential roles in TS to provide multiple directions for the future research on tics.
Topics: Animals; Histidine Decarboxylase; Humans; Mice; Mice, Knockout; Neurons; Tics; Tourette Syndrome
PubMed: 35114079
DOI: 10.1002/brb3.2511 -
Handbook of Experimental Pharmacology 2017While the normal functions of histamine (HA) in the central nervous system have gradually come into focus over the past 30 years, the relationship of abnormalities in... (Review)
Review
While the normal functions of histamine (HA) in the central nervous system have gradually come into focus over the past 30 years, the relationship of abnormalities in neurotransmitter HA to human disease has been slower to emerge. New insight came with the 2010 description of a rare nonsense mutation in the biosynthetic enzyme histidine decarboxylase (Hdc) that was associated with Tourette syndrome (TS) and related conditions in a single family pedigree. Subsequent genetic work has provided further support for abnormalities of HA signaling in sporadic TS. As a result of this genetic work, Hdc knockout mice, which were generated more than 15 years ago, have been reexamined as a model of the pathophysiology of TS and related conditions. Parallel work in these KO mice and in human carriers of the Hdc mutation has revealed abnormalities in the basal ganglia system and its modulation by dopamine (DA) and has confirmed the etiologic, face, and predictive validity of the model. The Hdc-KO model thus serves as a unique platform to probe the pathophysiology of TS and related conditions, and to generate specific hypotheses for subsequent testing in humans. This chapter summarizes the development and validation of this model and recent and ongoing work using it to further investigate pathophysiological changes that may contribute to these disorders.
Topics: Animals; Dopamine; Histamine; Histidine Decarboxylase; Humans; Mice; Mice, Knockout; Mutation; Tourette Syndrome
PubMed: 28233179
DOI: 10.1007/164_2016_127 -
Proceedings of the Japan Academy.... 2010Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in... (Review)
Review
Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse L-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE(2) receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.
Topics: Animals; Cloning, Molecular; DNA, Complementary; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Histamine; Histidine Decarboxylase; Homeostasis; Humans; Mice; Models, Biological; Receptors, Prostaglandin; Receptors, Prostaglandin E, EP3 Subtype
PubMed: 20948178
DOI: 10.2183/pjab.86.848 -
World Journal of Gastroenterology Dec 2015To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite.
AIM
To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite.
METHODS
Control tissues from fundus (n = 3) and corpus (n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours (GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2 (VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid (U-MeImAA) was determined using high-performance liquid chromatography in 27 of the 64 patients.
RESULTS
In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cell population co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-MeImAA excretion was detected, but only two of the patients exhibited related endocrine symptoms.
CONCLUSION
Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chromatography, High Pressure Liquid; Enterochromaffin Cells; Female; Fluorescent Antibody Technique; Ghrelin; Histidine Decarboxylase; Humans; Imidazoles; Male; Middle Aged; Neuroendocrine Cells; Neuroendocrine Tumors; Renal Elimination; Stomach Neoplasms; Urinalysis; Vesicular Monoamine Transport Proteins; Young Adult
PubMed: 26715806
DOI: 10.3748/wjg.v21.i47.13240