Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-kappaB Pathways in Nasal Fibroblasts
Allergy, Asthma & Immunology Research
; : 567-572, 2014.
Article
in En
| WPRIM
| ID: wpr-183727
Responsible library:
WPRO
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-kappaB, 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-kappaB induction. The H1R antagonist actively suppressed pp38 and NF-kappaB 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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Phosphotransferases
/
Enzyme-Linked Immunosorbent Assay
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Receptors, Histamine
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Histamine
/
Nose
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Blotting, Western
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Cytokines
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NF-kappa B
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Interleukin-6
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JNK Mitogen-Activated Protein Kinases
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Allergy, Asthma & Immunology Research
Year:
2014
Type:
Article