P2Y(6) Receptor-Mediated Proinflammatory Signaling in Human Bronchial Epithelia
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摘要P2Y receptors are expressed in virtually all epithelia and are responsible for the control of fluid and electrolyte transport. In asthmatic inflammation, the bronchial epithelia are damaged by eosinophil-derived, highly toxic cationic proteins, such as major basic protein (MBP). Consequently, extracellular nucleotides are released into the extracellular space from airway epithelial cells, and act in an autocrine or paracrine fashion to regulate immune functions. Our data show damage to the human bronchial epithelial cell line, 16HBE14o-, by poly-L-arginine-induced UDP release into the extracellular medium. Activation of P2Y(6) receptor by its natural ligand, UDP, or its specific agonist, MRS 2693, led to the production of two proinflammatory cytokines, interleukin (IL)-6 and IL-8. This may have resulted from increased IL-6 and IL-8 mRNA expression, and activation of p38 and ERK1/2 MAPK, and NF-kappa B pathways. Our previous study demonstrated that UDP stimulated transepithelial Cl- secretion via both Ca2+- and cAMP-dependent pathways in 16HBE14o- epithelia. This was further confirmed in this study by simultaneous imaging of Ca2+ and cAMP levels in single cells using the Fura-2 fluorescence technique and a FRET-based approach, respectively. Moreover, the P2Y(6) receptor-mediated production of IL-6 and IL-8 was found to be dependent on Ca2+, but not the cAMP/PKA pathway. Together, these studies show that nucleotides released during the airway inflammatory processes will activate P2Y(6) receptors, which will lead to further release of inflammatory cytokines. The secretion of cytokines and the formation of such "cytokine networks'' play an important role in sustaining the airway inflammatory disease.
著者Hao Y, Liang JF, Chow AW, Cheung WT, Ko WH
期刊名稱PLoS ONE
詳細描述To ORKTS: doi: 10.1371/journal.pone.0106235
出版年份2014
月份9
日期22
卷號9
期次9
出版社PUBLIC LIBRARY SCIENCE
國際標準期刊號1932-6203
語言英式英語
Web of Science 學科類別Multidisciplinary Sciences; Science & Technology - Other Topics

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