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KMID : 0900220200270020095
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대한비과학회지
2020 Volume.27 No. 2 p.95 ~ p.101
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Histamine Induced Production of Chemokine CXCL8 Through H1R/PLC and NF-κB Signaling Pathways in Nasal Fibroblasts
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Kang Byung-Jin
Park Joo-Hoo
Lee Heung-Man
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Abstract
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Background and Objectives: Histamine has been suggested to play an important role during allergic and inflammatory reactions, affecting allergic rhinitis and chronic rhinosinusitis. CXCL8 is a pro-inflammatory chemokine and a critical factor that causes many airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.
Materials and Method: Histamine cytotoxicity was measured by MTT assay. Real-time polymerase chain reaction was used to identify histamine type 1 receptor in nasal fibroblasts. The fibroblasts were then treated with histamine with or without a histamine type 1 receptor antagonist and the CXCL8 protein was assessed using an enzyme-linked immunosorbent assay (ELISA). The downstream signaling molecules, including phospholipase C and phospho-p50, were evaluated by western blot and immunofluorescent staining.
Results: Histamine had no significant cytotoxic effect until the concentration reached 1,000 μM. Histamine type 1 receptor mRNA was expressed in nasal fibroblasts. CXCL8 protein expression level was significantly increased following histamine stimulation. However, the expression level of CXCL8 decreased when phospholipase C was inhibited by U73122. Histamine increased phospho-p50 expression as seen in western blot results. The BAY11-7082, NF-κB inhibitor significantly reduced CXCL8 production in histamine-stimulated nasal fibroblasts.
Conclusion: Histamine can induce the production of NF-κB controlled-chemokine CXCL8 by nasal fibroblasts, which supports a role for histamine in upper airway inflammatory diseases.
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KEYWORD
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Histamine, CXCL8, Histamine type 1 receptor, Signal pathways, Nasal fibroblasts
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