Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-kappaB Pathways in Nasal Fibroblasts.
10.4168/aair.2014.6.6.567
- Author:
Il Ho PARK
1
;
Ji Young UM
;
Jung Sun CHO
;
Seung Hoon LEE
;
Sang Hag LEE
;
Heung Man LEE
Author Information
1. Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea. lhman@korea.ac.kr
- Publication Type:Original Article
- Keywords:
Nose;
fibroblast;
histamine;
IL-6;
allergic rhinitis
- MeSH:
Blotting, Western;
Cytokines;
Enzyme-Linked Immunosorbent Assay;
Fibroblasts*;
Histamine Antagonists;
Histamine*;
Humans;
Inflammation;
Interleukin-6*;
JNK Mitogen-Activated Protein Kinases;
Luciferases;
NF-kappa B*;
Nose;
Phosphotransferases;
Receptors, Histamine
- From:Allergy, Asthma & Immunology Research
2014;6(6):567-572
- CountryRepublic of Korea
- Language:English
-
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.
