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Publication : Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection.

First Author  Akthar S Year  2015
Journal  Nat Commun Volume  6
Pages  8423 PubMed ID  26400771
Mgi Jnum  J:227220 Mgi Id  MGI:5699933
Doi  10.1038/ncomms9423 Citation  Akthar S, et al. (2015) Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection. Nat Commun 6:8423
abstractText  Bioactive matrix fragments (matrikines) have been identified in a myriad of disorders, but their impact on the evolution of airway inflammation has not been demonstrated. We recently described a pathway where the matrikine and neutrophil chemoattractant proline-glycine-proline (PGP) could be degraded by the enzyme leukotriene A4 hydrolase (LTA4H). LTA4H classically functions in the generation of pro-inflammatory leukotriene B4, thus LTA4H exhibits opposing pro- and anti-inflammatory activities. The physiological significance of this secondary anti-inflammatory activity remains unknown. Here we show, using readily resolving pulmonary inflammation models, that loss of this secondary activity leads to more pronounced and sustained inflammation and illness owing to PGP accumulation. PGP elicits an exacerbated neutrophilic inflammation and protease imbalance that further degrades the extracellular matrix, generating fragments that perpetuate inflammation. This highlights a critical role for the secondary anti-inflammatory activity of LTA4H and thus has consequences for the generation of global LTA4H inhibitors currently being developed.
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