Αρχειοθήκη ιστολογίου

Πέμπτη 21 Σεπτεμβρίου 2017

Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration

Angiotensin converting enzyme 2 (ACE2) is a terminal carboxypeptidase with important functions in the renin angiotensin system and plays a critical role in inflammatory lung diseases. ACE2 cleaves single terminal residues from several bioactive peptides such as angiotensin II. However, few of its substrates in the respiratory tract have been identified and the mechanism underlying the role of ACE2 in inflammatory lung disease has not been fully characterized. In an effort to identify biological targets of ACE2 in the lung, we tested its effects on des-arg9 bradykinin (DABK) in airway epithelial cells based upon a hypothesis that DABK is a biological substrate of ACE2 in the lung and ACE2 plays an important role in the pathogenesis of acute lung inflammation partly through modulating DABK/BKB1R axis signaling. We found that loss of ACE2 function in mouse lung in the setting of endotoxin inhalation led to activation of the DABK/BKB1R (bradykinin receptor B1) axis, release of the proinflammatory chemokines such as CXCL5,MIP2, KC and TNF- MIP2 and TNF-a from airway epithelia, increased neutrophil infiltration and exaggerated lung inflammation and injury. These results indicate that a reduction in pulmonary ACE2 activity contributes to the pathogenesis of lung inflammation, in part due to an impaired ability to inhibit DABK/BKB1R axis mediated signaling, resulting in more prompt onset of neutrophil infiltration and more severe inflammation in the lung. Our study identifies a biological substrate of ACE2 within the airways, as well as a potential new therapeutic target for inflammatory diseases.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2fEvnin
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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