Histamine Type 2 Receptor Expression on Peripheral Blood Regulatory Lymphocytes in Patients with Allergic Rhinitis Treated with Specific Immunotherapy

Ciebiada, Maciej; Kasztalska, Karolina; Górska-Ciebiada, Małgorzata; Górski, Paweł

doi:10.2500/ajra.2014.28.4048

Cited by 8 publications

(7 citation statements)

References 37 publications

(76 reference statements)

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“…However, emerging evidence suggests that EoE is associated with IgG4, and not mediated by IgE[38]. Interestingly, patients with allergic rhinitis have increased H2R expressing regulatory T cells at the peak of pollen season [39]which points towards the possible role of food allergens in promoting HR expression during EoE. It is also not known if HR expression is regulated by Th2 cytokines such as IL5 and IL13 which are overexpressed during active inflammation in EoE.…”

Section: Discussionmentioning

confidence: 99%

Altered Esophageal Histamine Receptor Expression in Eosinophilic Esophagitis (EoE): Implications on Disease Pathogenesis

et al. 2015

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Eosinophilic Esophagitis (EoE) is a chronic allergic disorder, whose pathobiology is incompletely understood. Histamine-producing cells including mast cells and basophils have been implicated in EoE. However, very little is currently known about the role of histamine and histamine receptor (HR) expression and signaling in the esophageal epithelium. Herein, we characterized HR (H1R, H2R, H3R, and H4R) expression in human esophageal biopsies and investigate the role of histamine signaling in inducible cytokine expression in human esophageal epithelial cells in vitro. HR expression was quantified in esophageal biopsies from non-EoE control (N = 23), inactive EoE (<15 eos/hpf, N = 26) and active EoE (>15 eos/hpf, N = 22) subjects using qRT-PCR and immunofluorescent localization. HR expression and histamine-mediated cytokine secretion were evaluated in human primary and telomerase-immortalized esophageal epithelial cells. H1R, H2R, and H4R expression were increased in active EoE biopsies compared to inactive EoE and controls. H2R was the most abundantly expressed receptor, and H3R expression was negligible in all 3 cohorts. Infiltrating eosinophils expressed H1R, H2R, and H4R, which contributed to the observed increase in HR in active subjects. H1R and H2R, but not H3R or H4R, were constitutively expressed by primary and immortalized cells, and epithelial histamine stimulation induced GM-CSF, TNFα, and IL-8, but not TSLP or eotaxin-3 secretion. Epithelial priming with the TLR3 ligand poly (I:C) induced H1R and H2R expression, and enhanced histamine-induced GM-CSF, TNFα, and IL-8 secretion. These effects were primarily suppressed by H1R antagonists, but unaffected by H2R antagonism. Histamine directly activates esophageal epithelial cytokine secretion in vitro in an H1R dependent fashion. However, H1R, H2R and H4R are induced in active inflammation in EoE in vivo. While systemic antihistamine (anti-H1R) therapy may not induce clinical remission in EoE, our study suggests that further study of histamine receptor signaling in EoE is warranted and that targeting of additional histamine receptors may lead to novel treatment strategies for this important disease.

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Section: Discussionmentioning

confidence: 99%

Altered Esophageal Histamine Receptor Expression in Eosinophilic Esophagitis (EoE): Implications on Disease Pathogenesis

et al. 2015

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“…pathway', 'Inflammation mediated by chemokine and cytokine signaling pathway' and 'Histamine H2 receptor mediated signaling pathway' participate in allergic inflammation (4,(63)(64). 'Apoptosis signaling pathway' (65) and 'Toll receptor signaling pathway' (66) are also involved in the pathology of AR. The expression of endotherin 2 is increased in cigarette-exposed asthmatic mice (67).…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

HDAC inhibitor sodium butyrate prevents allergic rhinitis and alters lncRNA and mRNA expression profiles in the nasal mucosa of mice

et al. 2020

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Our previous study demonstrated that intranasal administration of histone deacetylase inhibitor sodium butyrate (NaB) exhibits therapeutic effects on a mouse model of allergic rhinitis (AR). However, whether NaB is effective on AR when administered orally and prophylactically, as well as its potential effects on gene expression, remained unknown. The present study aimed to investigate the preventive effect of NaB on AR when added to the diet of newly weaned mice and to evaluate the changes in long non-coding (lnc)RNA and mRNA expression profiles in the nasal mucosa. Mice were randomly divided into three groups as follows: i) control (c) group, (no treatment); ii) AR group [treated with ovalbumin (OVA)]; and iii) NaB + AR group (treated with OVA and NaB). The NaB + AR group was administered NaB in their feed (30 g/kg chow), whereas the other two groups were fed normal feed between 3 and 6 weeks of age. At 7 weeks of age, OVA administration was initiated to induce AR in the AR and NaB + AR groups. Following model establishment, behavioral assessments, western blotting and gene expression analysis were performed. NaB exhibited a preventive effect in the murine AR model, diminished the increases in histone deacetylase 1 (HdAc1) and HdAc8 expression and increased OVA-induced acetylation of histone H3 at lysine 9. In addition, NaB increased the AR-associated low expression of interleukin 2 (IL-2), interferon γ and IL-17 and decreased the expression of IL-4, IL-5 and transforming growth factor β1. Gene Ontology and pathway analyses revealed the top 10 pathways among the groups. Octamer-binding transcription factor 1, ecotropic viral integration site 1 and paired box 4 were predicted to be target genes of lncRNA (NONMMUT057309). Thus, NaB may exhibit a preventive effect on AR. Additionally, the lncRNA and mRNA expression profiles in the nasal mucosa of mice with AR differed significantly following NaB treatment. These results may provide insights into the pathogenesis of AR and suggest new treatment targets.

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“…mRNA expression studies confirmed the expression of H 1 , H 2 , and H 4 receptors whereas H 3 receptor mRNA was absent in CD8 + , CD4 + , and Th17 T cells 130–132 . The expression of H 2 receptor in Tregs from healthy subjects and patients with allergic rhinitis (AR) was demonstrated by flow cytometry 133 . Numerous studies evaluate the important role of histamine receptors using functional assays 114,115,133–138 (Figure 1).…”

Section: Histamine Modulation Of the Anti‐tumor Immunitymentioning

confidence: 87%

Histamine in cancer immunology and immunotherapy. Current status and new perspectives

Sarasola

Delgado

Nicoud

et al. 2021

Pharmacology Res & Perspec

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Cancer is the second leading cause of death globally and its incidence and mortality are rapidly increasing worldwide. The dynamic interaction of immune cells and tumor cells determines the clinical outcome of cancer. Immunotherapy comes to the forefront of cancer treatments, resulting in impressive and durable responses but only in a fraction of patients. Thus, understanding the characteristics and profiles of immune cells in the tumor microenvironment (TME) is a necessary step to move forward in the design of new immunomodulatory strategies that can boost the immune system to fight cancer. Histamine produces a complex and fine‐tuned regulation of the phenotype and functions of the different immune cells, participating in multiple regulatory responses of the innate and adaptive immunity. Considering the important actions of histamine‐producing immune cells in the TME, in this review we first address the most important immunomodulatory roles of histamine and histamine receptors in the context of cancer development and progression. In addition, this review highlights the current progress and foundational developments in the field of cancer immunotherapy in combination with histamine and pharmacological compounds targeting histamine receptors.

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Histamine Type 2 Receptor Expression on Peripheral Blood Regulatory Lymphocytes in Patients with Allergic Rhinitis Treated with Specific Immunotherapy

Cited by 8 publications

References 37 publications

Altered Esophageal Histamine Receptor Expression in Eosinophilic Esophagitis (EoE): Implications on Disease Pathogenesis

Altered Esophageal Histamine Receptor Expression in Eosinophilic Esophagitis (EoE): Implications on Disease Pathogenesis

HDAC inhibitor sodium butyrate prevents allergic rhinitis and alters lncRNA and mRNA expression profiles in the nasal mucosa of mice

Histamine in cancer immunology and immunotherapy. Current status and new perspectives

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