Potentiation of NF-κB-dependent transcription and inflammatory mediator release by histamine in human airway epithelial cells
| Autor: | Holden, N S, Gong, W, King, E M, Kaur, M, Giembycz, M A, Newton, R |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Interleukin-6
Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Blotting Western Genetic Vectors Interleukin-8 Anti-Inflammatory Agents Histamine Antagonists NF-kappa B Gene Expression Bronchi Epithelial Cells Research Papers Dexamethasone Adenoviridae Cell Line Humans Receptors Histamine I-kappa B Proteins Inflammation Mediators Cells Cultured Histamine |
| Popis: | In asthma, histamine contributes to bronchoconstriction, vasodilatation and oedema, and is associated with the late phase response. The current study investigates possible inflammatory effects of histamine acting on nuclear factor kappaB (NF-kappaB)-dependent transcription and cytokine release.Using BEAS-2B bronchial epithelial cells, NF-kappaB-dependent transcription and both release and mRNA expression of IL-6 and IL-8 were examined by reporter assay, ELISA and quantitative RT-PCR. Histamine receptors were detected using qualitative RT-PCR and function examined using selective agonists and antagonists.Addition of histamine to TNFalpha-stimulated BEAS-2B cells maximally potentiated NF-kappaB-dependent transcription 1.8 fold, whereas IL-6 and IL-8 protein release were enhanced 7.3- and 2.7-fold respectively. These responses were, in part, NF-kappaB-dependent and were associated with 2.6- and 1.7-fold enhancements of IL-6 and IL-8 mRNA expression. The H(1) receptor antagonist, mepyramine, caused a rightward shift in the concentration-response curves of TNFalpha-induced NF-kappaB-dependent transcription (pA(2)=9.91) and release of IL-6 (pA(2)=8.78) and IL-8 (pA(2)=8.99). Antagonists of histamine H(2), H(3) and H(4) receptors were without effect. Similarly, H(3) and H(4) receptor agonists did not affect TNFalpha-induced NF-kappaB-dependent transcription, or IL-6 and IL-8 release at concentrations below 10 microM. The anti-inflammatory glucocorticoid, dexamethasone, inhibited the histamine enhanced NF-kappaB-dependent transcription and IL-6 and IL-8 release.Potentiation of NF-kappaB-dependent transcription and inflammatory cytokine release by histamine predominantly involves receptors of the H(1) receptor subtype. These data support an anti-inflammatory role for H(1) receptor antagonists by preventing the transcription and release of pro-inflammatory cytokines. |
| Databáze: | OpenAIRE |
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