Localization and Upregulation of the Nasal Histamine H1 Receptor in Perennial Allergic Rhinitis

Shirasaki, Hideaki; Kanaizumi, Etsuko; Seki, Nobuhiko; Himi, Tetsuo

doi:10.1155/2012/951316

Cited by 23 publications

(18 citation statements)

References 24 publications

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“…As histamine-1 receptor (H1R) antagonists control symptoms related to histamine expression, H1R is generally accepted as the primary receptor of histamine activity. An immunohistochemical study demonstrated intense immunoreactivity for H1R in nasal epithelial cells and vascular endothelial cells 3. Furthermore, it has been shown that histamine affects vascular permeability, allowing for leukocyte infiltration and edema formation via H1R 4.…”

Section: Introductionmentioning

confidence: 99%

Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-κB Pathways in Nasal Fibroblasts

Park

Cho

et al. 2014

Allergy Asthma Immunol Res

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PurposeBased on the close relationship between histamine and interleukin 6 (IL-6), we hypothesized that histamine may regulate the production of cytokines, such as IL-6, during allergic inflammation. Here, we examined the role of histamine in IL-6 production and histamine receptor activity in nasal fibroblasts, along with the mechanisms underlying these effects.MethodsExperiments were performed using nasal fibroblasts from 8 normal patients. RT-PCR was used to identify the major histamine receptors expressed in nasal fibroblasts. Fibroblasts were then treated with histamine with or without histamine-receptor antagonists, and monitored for IL-6 production using an ELISA. Four potential downstream signaling molecules, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB, were evaluated by Western blot, and a luciferase reporter assay.ResultsElevated expression was seen for all histamine receptors, with IL-6 protein levels increasing significantly following histamine stimulation. Among the histamine-receptor specific antagonists, only the H1R antagonist significantly decreased IL-6 production in histamine-stimulated nasal fibroblasts. Histamine increased the expression level of phosphorylated p38 (pp38), pERK, and pJNK, as well as NF-κB induction. The H1R antagonist actively suppressed pp38 and NF-κB expression in histamine-induced nasal fibroblasts, but not pERK and pJNK. The p38 inhibitor strongly attenuated IL-6 production in histamine-stimulated nasal fibroblasts.ConclusionsThe data presented here suggest that antihistamines may be involved in the regulation of cytokines, such as IL-6, due to the role of histamine as an inflammatory mediator in nasal fibroblasts.

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Section: Introductionmentioning

confidence: 99%

Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-κB Pathways in Nasal Fibroblasts

Park

Cho

et al. 2014

Allergy Asthma Immunol Res

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“…Histamine is also stored in large amounts in secretory glands. It is involved in the elicitation of immediate-type allergic reactions as well as in tissue remodeling and chronic inflammation [ 2 , 3 ] by binding to one of the four known G-protein coupled transmembrane H1–H4 receptors. These receptors are expressed on various cell types including monocytes, lymphocytes, dendritic cells, and keratinocytes [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Amarogentin Displays Immunomodulatory Effects in Human Mast Cells and Keratinocytes

Wölfle

Haarhaus

Schempp

2015

Mediators of Inflammation

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Keratinocytes express the bitter taste receptors TAS2R1 and TAS2R38. Amarogentin as an agonist for TAS2R1 and other TAS2Rs promotes keratinocyte differentiation. Similarly, mast cells are known to express bitter taste receptors. The aim of this study was to assess whether bitter compounds display immunomodulatory effects on these immunocompetent cells in the skin, so that they might be a target in chronic inflammatory diseases such as atopic dermatitis and psoriasis. Here, we investigated the impact of amarogentin on substance P-induced release of histamine and TNF-α from the human mast cell line LAD-2. Furthermore, the effect of amarogentin on HaCaT keratinocytes costimulated with TNF-α and histamine was investigated. Amarogentin inhibited in LAD-2 cells substance P-induced production of newly synthesized TNF-α, but the degranulation and release of stored histamine were not affected. In HaCaT keratinocytes histamine and TNF-α induced IL-8 and MMP-1 expression was reduced by amarogentin to a similar extent as with azelastine. In conclusion amarogentin displays immunomodulatory effects in the skin by interacting with mast cells and keratinocytes.

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“…Few studies have evaluated HRH1 expression among those with asthma and/or allergic disease (37, 38) . We have previously shown that HRH1 mRNA expression was significantly up-regulated in adults (p=0.04) with asthma compared to those without asthma (10) .…”

Section: Discussionmentioning

confidence: 99%

Genetic variation within the histamine pathway among patients with asthma – a pilot study

et al. 2014

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Objective Histamine is an important mediator in the pathophysiology of asthma. We have previously reported that HRH1 is differentially expressed among those with asthma compared to those without asthma. Single histamine related genes have also been associated with asthma. We aimed to evaluate known single nucleotide polymorphisms (SNPs) in genes along the histamine biotransformation and response pathway and determine their association with asthma and HRH1 mRNA expression. Methods We enrolled children and adults (n=93) with/without asthma who met inclusion/exclusion criteria. Genotyping was performed for 9 known SNPs in the HDC, HRH1, HRH4, HNMT, and ABP1 genes. HRH1 mRNA expression was determined on RNA from buccal tissue. General linear model, Fisher's exact test, and Chi-square test were used to determine differences in allele, genotype, and haplotype frequency between subjects with and without asthma and differential HRH1 mRNA expression relative to genotype. Statistical significance was determined by p<0.05. Results No difference was observed in genotype/allele frequency for the 9 SNPs between subjects with and without asthma. The HNMT-1639C/ −464C/ 314C/ 3’UTRA haplotype was more frequently observed in those without asthma than those with asthma (p=0.03). We also observed genetic differences relative to race and gender. HNMT 314 genotype CT was more frequent in males with asthma compared to those without asthma (p=0.04). Conclusions Histamine pathway haplotype was associated with a diagnosis of asthma in our cohort but allele and genotype were not. Subgroup evaluations may also be important. Further studies are needed to determine the potential biological/clinical significance of our findings.

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Localization and Upregulation of the Nasal Histamine H1 Receptor in Perennial Allergic Rhinitis

Cited by 23 publications

References 24 publications

Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-κB Pathways in Nasal Fibroblasts

Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-κB Pathways in Nasal Fibroblasts

Amarogentin Displays Immunomodulatory Effects in Human Mast Cells and Keratinocytes

Genetic variation within the histamine pathway among patients with asthma – a pilot study

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