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
Dans Anglais
| WPRIM
| ID: wpr-183727
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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Phosphotransferases
/
Test ELISA
/
Récepteurs histaminergiques
/
Histamine
/
Nez
/
Technique de Western
/
Cytokines
/
Facteur de transcription NF-kappa B
/
Interleukine-6
/
JNK Mitogen-Activated Protein Kinases
Type d'étude:
Étude pronostique
Limites du sujet:
Humains
langue:
Anglais
Texte intégral:
Allergy, Asthma & Immunology Research
Année:
2014
Type:
Article
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