The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines

Thurmond, Robin L.; Gelfand, Erwin W.; Dunford, Paul J.

doi:10.1038/nrd2465

Cited by 496 publications

(493 citation statements)

References 175 publications

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“…In a mouse model of zymosan-induced peritonitis, histamine H 4 R ligands exerted anti-inflammatory activity [41,42]. In this model, intra-peritoneal treatment of mice with zymosan induces neutrophil migration, which is blocked by an H 4 R antagonist [43]. Accumulating experimental evidence indicates the role of H 4 R in modulating lung inflammation, mainly through its effects on Th2 cell induction [44].…”

Section: Discussionmentioning

confidence: 99%

Role of histamine H 4 receptor ligands in bleomycin-induced pulmonary fibrosis

Lucarini

Pini

Rosa

et al. 2016

Pharmacological Research

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Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The results here reported clearly demonstrated that H 4 R ligands have a beneficial effect in a model of lung fibrosis in the mouse, thus indicating that H 4 R antagonists or inverse agonists could be a novel therapeutic strategy for lung inflammatory diseases.4

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Section: Discussionmentioning

confidence: 99%

Role of histamine H 4 receptor ligands in bleomycin-induced pulmonary fibrosis

Lucarini

Pini

Rosa

et al. 2016

Pharmacological Research

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“…Histamine plays a critical role in various physiological responses, such as inflammation, gastric acid secretion, neurotransmission, and immune modulation, which are mediated by its specific receptors, the H 1 , H 2 , H 3 , and H 4 subtypes [1][2][3][4]. Mast cells are the primary sources of tissue histamine and it is liberated from the cytoplasmic granules upon various stimuli including IgE-dependent Ag stimulation [5].…”

Section: Introductionmentioning

confidence: 99%

Histamine synthesis is required for granule maturation in murine mast cells

et al. 2013

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Mast cells are the major sources of histamine, which is released in response to immunological stimulations. The synthesis of histamine is catalyzed by histidine decarboxylase (HDC). Previous studies have shown that Hdc −/− mast cells exhibit aberrant granule morphology with severely decreased granule content. Here, we investigated whether the histamine synthesized in mast cells regulates the granule maturation of murine mast cells. Several genes, including those encoding granule proteases and enzymes involved in heparin biosynthesis, were downregulated in Hdc −/− peritoneal mast cells. Impaired granule maturation was also found in Hdc −/− BM-derived cultured mast cells when they were cocultured with fibroblasts in the presence of c-kit ligand. Exogenous application of histamine and several H 4 receptor agonists restored the granule maturation of Hdc −/− cultured mast cells. However, the maturation of granules was largely normal in Hrh4 −/− peritoneal mast cells. Depletion of cellular histamine with tetrabenazine, an inhibitor of vesicular monoamine transporter-2, did not affect granule maturation. In vivo experiments with mast cell deficient Kit W /Kit W-v mice indicated that the expression of the Hdc gene in mast cells is required for granule maturation. These results suggest that histamine promotes granule maturation in mast cells and acts as an proinflammatory mediator. [6,7]. In a mouse mastocytoma P-815 cells, caspase-9-mediated cleavage results in enzymatic activation of HDC [8]. KeywordsWe have explored novel functions of histamine using a mouse strain lacking the Hdc gene. In the first report of Hdc −/− mice, we noticed that peritoneal mast cells (pMCs) and skin mast cells exhibited an aberrant morphology with severely decreased granule contents [9]. Although several studies indicated that mast cells express specific histamine receptors, it remains unknown how histamine affects the nature of mast cells. On the other hand, positive modulators for growth and differentiation of mast cells, such as IL-3 and c-kit ligand (Kitl), were found to induce a transient increase in histamine synthesis [10,11], raising a possibility that histamine is involved in the process of mast cell maturation. We hypothesized that newly synthesized histamine may play a critical role in granule maturation of mast cells in an autocrine fashion. We, here, took two different approaches to investigate the mechanism underlying the histamine-mediated promotion of granule maturation of mast cells; an in vitro approach using a mast cell fibroblast coculture model and an in vivo one using the mast cell reconstitution system with mast cell deficient Kit W /Kit W-v mice. This study proposes a novel function of histamine in mast cell biology. Results Characterization of the pMCs in Hdc −/− miceWe previously reported that the cutaneous and pMCs of Hdc −/− mice demonstrate aberrant granules with severely decreased contents [9]. pMCs in Hdc −/− mice were poorly-stained with Safranin-O and acidic Toluidine blue, compared with those in WT mice (Fi...

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“…Histamine is a potent agonist of all four receptors (H1-H4) [6,13,14] that are distributed in different parts of body. These receptors modulate different biochemical, pharmacological and immunological reactions, both in vivo and in vitro, by activating signal transduction pathways for endogenous histamine release [13].…”

Section: Immunomodulatory Profile By H1 and H2 Agonists And Antagonistsmentioning

confidence: 99%

“…Histamine receptor type 1 (H1R) and histamine receptor type 2 (H2R) both belong to the G-protein-coupled receptor family [13]; however, they trigger different biochemical intracellular events upon activation [13,14]. H1Rs and H2Rs are also regulated by specific cytokines present in the immune system.…”

Section: Introductionmentioning

confidence: 99%

Modulation of in vivo immunoglobulin production by endogenous histamine and H1R and H2R agonists and antagonists

Tripathi

Shahid

Khan

et al. 2010

Pharmacological Reports

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Abstract:The present study was designed to delineate the immunomodulatory role of histamine receptors (H1R and H2R) and their antibody generation in a rabbit model. Six groups containing 18 rabbits each received either vehicle (sterile distilled water, 1 ml/kg × b.i. 14, 21, 28 and 58 (post-immunization). Both the ELISA and the HA showed similar production of Igs, IgM and IgG but the results were found comparatively more significant by ELISA as opposed to HA. Results showed that histamine could influence a detectable antibody response to SRBC early (i.e

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The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines

Cited by 496 publications

References 175 publications

Role of histamine H 4 receptor ligands in bleomycin-induced pulmonary fibrosis

Role of histamine H 4 receptor ligands in bleomycin-induced pulmonary fibrosis

Histamine synthesis is required for granule maturation in murine mast cells

Modulation of in vivo immunoglobulin production by endogenous histamine and H1R and H2R agonists and antagonists

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