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

Park IH, Um JY, Cho JS, Lee SH, Lee SH, Lee HM - Allergy Asthma Immunol Res (2014)

Bottom Line: 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.Among the histamine-receptor specific antagonists, only the H1R antagonist significantly decreased IL-6 production in histamine-stimulated nasal fibroblasts.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea.

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.

No MeSH data available.


A dose-response analysis of H1R antagonist fexofenadine on IL-6 production was determined by ELISA. Values are expressed as the means±SE of independent experiments. *P<0.05 vs control.
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Figure 4: A dose-response analysis of H1R antagonist fexofenadine on IL-6 production was determined by ELISA. Values are expressed as the means±SE of independent experiments. *P<0.05 vs control.

Mentions: To identify the histamine receptors involved in IL-6 production, nasal fibroblasts were pretreated with histamine receptor antagonists for H1R (fexofenadine, 100 µM), H2R (ranitidine, 50 µM), H3R (clobenpropit, 50 µM), and H4R (JNJ7777120, 100 µM) for 2 hours, and then stimulated with histamine (100 µM) for 24 hours. Fexofenadine significantly decreased IL-6 production, whereas ranitidine, clobenpropit, and JNJ7777120 had no effect (Fig. 3). These assays were then expanded to assess the role of fexofenadine concentration on IL-6 production. Cells were pretreated with 1, 10, or 100 µM fexofenadine for 1 hour and then stimulated with histamine (100 µM) for 24 hours. Fexofenadine inhibited the expression of IL-6 protein in a dose-dependent manner (Fig. 4).


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

Park IH, Um JY, Cho JS, Lee SH, Lee SH, Lee HM - Allergy Asthma Immunol Res (2014)

A dose-response analysis of H1R antagonist fexofenadine on IL-6 production was determined by ELISA. Values are expressed as the means±SE of independent experiments. *P<0.05 vs control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214978&req=5

Figure 4: A dose-response analysis of H1R antagonist fexofenadine on IL-6 production was determined by ELISA. Values are expressed as the means±SE of independent experiments. *P<0.05 vs control.
Mentions: To identify the histamine receptors involved in IL-6 production, nasal fibroblasts were pretreated with histamine receptor antagonists for H1R (fexofenadine, 100 µM), H2R (ranitidine, 50 µM), H3R (clobenpropit, 50 µM), and H4R (JNJ7777120, 100 µM) for 2 hours, and then stimulated with histamine (100 µM) for 24 hours. Fexofenadine significantly decreased IL-6 production, whereas ranitidine, clobenpropit, and JNJ7777120 had no effect (Fig. 3). These assays were then expanded to assess the role of fexofenadine concentration on IL-6 production. Cells were pretreated with 1, 10, or 100 µM fexofenadine for 1 hour and then stimulated with histamine (100 µM) for 24 hours. Fexofenadine inhibited the expression of IL-6 protein in a dose-dependent manner (Fig. 4).

Bottom Line: 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.Among the histamine-receptor specific antagonists, only the H1R antagonist significantly decreased IL-6 production in histamine-stimulated nasal fibroblasts.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea.

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.

No MeSH data available.