MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity: A new perspective for the treatment

摘要: Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, bacterial viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these lead to development AHR limited. Activation intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-kappa B) their related signal pathways including C (PKC), phosphoinositide 3-kinase (PI3K) A (PKA) signaling may result in airway kinin receptor upregulation, which suggested play an important role AHR. Environmental trigger production pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) interleukins (ILs) that activate MAPK- NF-kappa B-dependent pathways, subsequently via upregulation. Blockage MAPK/NF-kappa prevents B-1 B-2 expression airways, resulting decrease response bradykinin (kinin agonist) des-Arg(9)-bradykinin agonist). This suggests upregulation can provide novel option treatment well other diseases. (C) 2013 Elsevier Ltd. All rights reserved. (Less)