MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity: a new perspective for the treatment
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MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity : a new perspective for the treatment. / Zhang, Yaping; Cardell, Lars-Olaf; Edvinsson, Lars; Xu, Cang-Bao.
In: Pharmacological Research, Vol. 71, 05.2013, p. 9-18.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity
T2 - a new perspective for the treatment
AU - Zhang, Yaping
AU - Cardell, Lars-Olaf
AU - Edvinsson, Lars
AU - Xu, Cang-Bao
N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.
PY - 2013/5
Y1 - 2013/5
N2 - Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, and bacterial and viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these risk factors lead to the development of AHR is limited. Activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) and their related signal pathways including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and protein kinase A (PKA) signaling pathways may result in airway kinin receptor upregulation, which is suggested to play an important role in the development of AHR. Environmental risk factors trigger the production of pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukins (ILs) that activate intracellular MAPK- and NF-κB-dependent inflammatory pathways, which subsequently lead to AHR via kinin receptor upregulation. Blockage of intracellular MAPK/NF-κB signaling prevents kinin B₁ and B₂ receptor expression in the airways, resulting in a decrease in the response to bradykinin (kinin B₂ receptor agonist) and des-Arg⁹-bradykinin (kinin B₁ receptor agonist). This suggests that MAPK- and NF-κB-dependent kinin receptor upregulation can provide a novel option for treatment of AHR in asthmatic as well as in other inflammatory airway diseases.
AB - Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, and bacterial and viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these risk factors lead to the development of AHR is limited. Activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) and their related signal pathways including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and protein kinase A (PKA) signaling pathways may result in airway kinin receptor upregulation, which is suggested to play an important role in the development of AHR. Environmental risk factors trigger the production of pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukins (ILs) that activate intracellular MAPK- and NF-κB-dependent inflammatory pathways, which subsequently lead to AHR via kinin receptor upregulation. Blockage of intracellular MAPK/NF-κB signaling prevents kinin B₁ and B₂ receptor expression in the airways, resulting in a decrease in the response to bradykinin (kinin B₂ receptor agonist) and des-Arg⁹-bradykinin (kinin B₁ receptor agonist). This suggests that MAPK- and NF-κB-dependent kinin receptor upregulation can provide a novel option for treatment of AHR in asthmatic as well as in other inflammatory airway diseases.
U2 - 10.1016/j.phrs.2013.02.004
DO - 10.1016/j.phrs.2013.02.004
M3 - Journal article
C2 - 23428345
VL - 71
SP - 9
EP - 18
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
ER -
ID: 48442028