Histamine promotes the release of interleukin-6 via the H1R/p38 and NF-κB pathways in nasal fibroblasts

Il Ho Park, Ji Young Um, Jung Sun Cho, Seung Hoon Lee, Sang Hag Lee, Heung Man Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: Based 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. Methods: Experiments 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. Results: Elevated 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. Conclusions: The 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.

Original languageEnglish
Pages (from-to)567-572
Number of pages6
JournalAllergy, Asthma and Immunology Research
Volume6
Issue number6
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Histamine Release
Nose
Histamine
Interleukin-6
Fibroblasts
Histamine Receptors
Histamine Antagonists
Cytokines
Interleukin-6 Receptors
JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Luciferases
Western Blotting
Enzyme-Linked Immunosorbent Assay
Inflammation
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

Cite this

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title = "Histamine promotes the release of interleukin-6 via the H1R/p38 and NF-κB pathways in nasal fibroblasts",
abstract = "Purpose: Based 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. Methods: Experiments 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. Results: Elevated 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. Conclusions: The 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.",
keywords = "Allergic rhinitis, Fibroblast, Histamine, IL-6, Nose",
author = "Park, {Il Ho} and Um, {Ji Young} and Cho, {Jung Sun} and Lee, {Seung Hoon} and Lee, {Sang Hag} and Lee, {Heung Man}",
year = "2014",
month = "1",
day = "1",
doi = "10.4168/aair.2014.6.6.567",
language = "English",
volume = "6",
pages = "567--572",
journal = "Allergy, Asthma and Immunology Research",
issn = "2092-7355",
publisher = "Korean Academy of Asthma, Allergy and Clinical Immunology",
number = "6",

}

TY - JOUR

T1 - Histamine promotes the release of interleukin-6 via the H1R/p38 and NF-κB pathways in nasal fibroblasts

AU - Park, Il Ho

AU - Um, Ji Young

AU - Cho, Jung Sun

AU - Lee, Seung Hoon

AU - Lee, Sang Hag

AU - Lee, Heung Man

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Purpose: Based 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. Methods: Experiments 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. Results: Elevated 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. Conclusions: The 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.

AB - Purpose: Based 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. Methods: Experiments 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. Results: Elevated 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. Conclusions: The 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.

KW - Allergic rhinitis

KW - Fibroblast

KW - Histamine

KW - IL-6

KW - Nose

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U2 - 10.4168/aair.2014.6.6.567

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JO - Allergy, Asthma and Immunology Research

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