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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.


Effect of p38 inhibition on IL-6 production in histamine-stimulated nasal fibroblasts. Values are expressed as the means±S.E. *P<0.05 vs control. †P<0.05 vs histamine alone.
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Figure 6: Effect of p38 inhibition on IL-6 production in histamine-stimulated nasal fibroblasts. Values are expressed as the means±S.E. *P<0.05 vs control. †P<0.05 vs histamine alone.

Mentions: Next, we confirmed the effect of p38 inhibition on IL-6 production in histamine-stimulated nasal fibroblasts by ELISA. Cells were pretreated with fexofenadine for 1 hour, and then stimulated with histamine for 24 hours. Increased expression of IL-6 following histamine-stimulation was markedly suppressed in the presence of 30 µM SB203580 (Fig. 6). Neither U0126 nor SP600125 inhibited IL-6 production in histamine-stimulated nasal fibroblasts, consistent with our Western blot results.


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)

Effect of p38 inhibition on IL-6 production in histamine-stimulated nasal fibroblasts. Values are expressed as the means±S.E. *P<0.05 vs control. †P<0.05 vs histamine alone.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Effect of p38 inhibition on IL-6 production in histamine-stimulated nasal fibroblasts. Values are expressed as the means±S.E. *P<0.05 vs control. †P<0.05 vs histamine alone.
Mentions: Next, we confirmed the effect of p38 inhibition on IL-6 production in histamine-stimulated nasal fibroblasts by ELISA. Cells were pretreated with fexofenadine for 1 hour, and then stimulated with histamine for 24 hours. Increased expression of IL-6 following histamine-stimulation was markedly suppressed in the presence of 30 µM SB203580 (Fig. 6). Neither U0126 nor SP600125 inhibited IL-6 production in histamine-stimulated nasal fibroblasts, consistent with our Western blot results.

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.