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Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides

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Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides : mechanism of KPV action and a role for MC3R agonists. / Land, Stephen C.

In: International Journal of Physiology, Pathophysiology and Pharmacology, Vol. 4, No. 2, 2012, p. 59-73.

Research output: Contribution to journalArticle

Harvard

Land, SC 2012, 'Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists' International Journal of Physiology, Pathophysiology and Pharmacology, vol 4, no. 2, pp. 59-73.

APA

Land, S. C. (2012). Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists. International Journal of Physiology, Pathophysiology and Pharmacology, 4(2), 59-73

Vancouver

Land SC. Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists. International Journal of Physiology, Pathophysiology and Pharmacology. 2012;4(2):59-73.

Author

Land, Stephen C. / Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides : mechanism of KPV action and a role for MC3R agonists.

In: International Journal of Physiology, Pathophysiology and Pharmacology, Vol. 4, No. 2, 2012, p. 59-73.

Research output: Contribution to journalArticle

Bibtex - Download

@article{75e38642b53e48aa99375be3153aeacc,
title = "Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides",
author = "Land, {Stephen C.}",
year = "2012",
volume = "4",
number = "2",
pages = "59--73",
journal = "International Journal of Physiology, Pathophysiology and Pharmacology",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides

T2 - mechanism of KPV action and a role for MC3R agonists

A1 - Land,Stephen C.

AU - Land,Stephen C.

PY - 2012

Y1 - 2012

N2 - Background/Aims: Chemokine signaling from airway epithelium regulates macrophage recruitment to the lung in inflammatory diseases such as asthma. This study investigates the mechanism by which the a-melanocyte stimulating hormone-derived tripeptide, KPV, and the agonist of the dominant melanocortin receptor in airway epithelium (MC3R), ?-melanocyte stimulating hormone (?-MSH), suppress inflammation in immortalised human bronchial airway epithelium. Methods: TNFa and rhino syncitial virus (RSV)-evoked nuclear factor-?B (NF?B) signaling was measured in immortalised human bronchial epithelial cells (16HBE14o-) in response to KPV and ?MSH. Cellular and systemic inflammatory signaling was measured by NF?B reporter gene and chemokine (IL8, eotaxin) secretion, respectively. Results: KPV and ?MSH evoked a dose-dependent inhibition of NF?B, matrix metalloproteinase-9 activity, IL8 and eotaxin secretion. The KPV effect was associated with its nuclear import, I?Ba stabilisation and suppressed nuclear translocation of YFP-tagged p65RelA. Competition assays revealed an interaction between KPV and the Imp- a3 binding site on p65RelA which may involve blockade of the importin-a armadillo domain 7 and 8. In contrast, the ?MSH anti-inflammatory effect required MC3R whose apical expression occurred in epithelium distributed along the length of the respiratory tree in vivo. Conclusion: KPV and ?MSH respectively suppress NF?B signalling in airway epithelium by: i) inhibition of p65RelA nuclear import and, ii) epithelial MC3R activation. Melanocortin peptides therefore provide a robust mechanism for targeting airway inflammation in lung disease.

AB - Background/Aims: Chemokine signaling from airway epithelium regulates macrophage recruitment to the lung in inflammatory diseases such as asthma. This study investigates the mechanism by which the a-melanocyte stimulating hormone-derived tripeptide, KPV, and the agonist of the dominant melanocortin receptor in airway epithelium (MC3R), ?-melanocyte stimulating hormone (?-MSH), suppress inflammation in immortalised human bronchial airway epithelium. Methods: TNFa and rhino syncitial virus (RSV)-evoked nuclear factor-?B (NF?B) signaling was measured in immortalised human bronchial epithelial cells (16HBE14o-) in response to KPV and ?MSH. Cellular and systemic inflammatory signaling was measured by NF?B reporter gene and chemokine (IL8, eotaxin) secretion, respectively. Results: KPV and ?MSH evoked a dose-dependent inhibition of NF?B, matrix metalloproteinase-9 activity, IL8 and eotaxin secretion. The KPV effect was associated with its nuclear import, I?Ba stabilisation and suppressed nuclear translocation of YFP-tagged p65RelA. Competition assays revealed an interaction between KPV and the Imp- a3 binding site on p65RelA which may involve blockade of the importin-a armadillo domain 7 and 8. In contrast, the ?MSH anti-inflammatory effect required MC3R whose apical expression occurred in epithelium distributed along the length of the respiratory tree in vivo. Conclusion: KPV and ?MSH respectively suppress NF?B signalling in airway epithelium by: i) inhibition of p65RelA nuclear import and, ii) epithelial MC3R activation. Melanocortin peptides therefore provide a robust mechanism for targeting airway inflammation in lung disease.

UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84863952469&md5=9d59998174ce4d17dcd7f6861fa4b9e5

UR - http://www.ijppp.org/contents.html

M1 - Article

JO - International Journal of Physiology, Pathophysiology and Pharmacology

JF - International Journal of Physiology, Pathophysiology and Pharmacology

IS - 2

VL - 4

SP - 59

EP - 73

ER -

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