KMID : 1225720140060060567
|
|
Allergy, Asthma & Immunology Research : AAIR 2014 Volume.6 No. 6 p.567 ~ p.572
|
|
Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-¥êB Pathways in Nasal Fibroblasts
|
|
Park Il-Ho
Um Ji-Young Cho Jung-Sun Lee Seung-Hoon Lee Sang-Hag Lee Heung-Man
|
|
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-¥êB, 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-¥êB induction. The H1R antagonist actively suppressed pp38 and NF-¥êB 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.
|
|
KEYWORD
|
|
Nose, fibroblast, histamine, IL-6, allergic rhinitis
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|