Potentiation of NF-κB-dependent transcription and inflammatory mediator release by histamine in human airway epithelial cells

Holden, Neil S. and Gong, W. and King, E. M. and Kaur, M. and Giembycz, M. A. and Newton, R. (2007) Potentiation of NF-κB-dependent transcription and inflammatory mediator release by histamine in human airway epithelial cells. British journal of pharmacology, 152 (6). pp. 891-902. ISSN 0007-1188

Full content URL: http://dx.doi.org/10.1038/sj.bjp.0707457

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Potentiation of NF-κB-dependent transcription and inflammatory mediator release by histamine in human airway epithelial cells

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Abstract

BACKGROUND AND PURPOSE

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.

EXPERIMENTAL APPROACH

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.

KEY RESULTS

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.

CONCLUSIONS AND IMPLICATIONS

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.

Keywords:BEAS-2B epithelial cells, Glucocorticoid, Histamine, IL-6, IL-8, Inflammation, Mepyramine, NF-?B
Subjects:B Subjects allied to Medicine > B210 Pharmacology
Divisions:College of Science > School of Life Sciences
ID Code:15126
Deposited On:19 Nov 2014 16:42

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