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lördag 9 december 2017

(2015) Astma, 15-HETE ja eoxiinit . Eoxiini C4, EXC4

Allergisessa astmassa  eräs  vaikuttaja 15-HETE ja eoxiini C4, EXC4


Pe  8.12. 2017 sain kirjastosta tämän  Karoliinisen instituutin  artikkelin  vuodelta 2015 kokonaisuudessaan:
Siinä on kuvattu molekyyli  EXC4, eoxiini C4.

Original Research Article
On the biosynthesis of 15-HETE and eoxin C4 by human airway epithelial cells
Åsa Brunnström
Erik Andersson
Helene Leksell
Bengt Mannervik
Barbro Dahléne
Hans-Erik Claessona


• Primary human airway epithelial cells have high expression of 15-LO-1.
• Primary human airway epithelial cells can produce EXC4.
• Airway epithelial cells produce increased amounts of 15-HETE after bacterial infection.
• Conversion of EXA4 to EXC4 is catalyzed by soluble GSTs in epithelial cells.
• Bronchial biopsies demonstrated co-expression of 15-LO-1 and GST P1-1.

Several lines of evidence indicate that 15-lipoxygenase type 1 (15-LO-1) plays
a pathophysiological role in asthma.

The aim for this study was to investigate the 15-LO-1 expression and activity
in primary human airway epithelial cells cultivated on micro-porous filters at
air–liquid interface. Incubation of human airway epithelial cells with arachidonic acid led to the formation of
15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and
 exposing the cells to
 bacteria or physical injury markedly increased their production of 15-HETE.

 The cells were also found to convert arachidonic acid to eoxin C4 (EXC4).
Subcellular fractionation revealed that the conversion of EXA4 to EXC4 was
 catalyzed by a soluble glutathione transferase (GST). The GST P1-1 enzyme
was found to possess the highest activity of the investigated soluble GSTs.

 Following IL-4 treatment of airway epithelial cells, microarray analysis
confirmed high expression of 15-LO-1 and GST P1-1, and immunohistochemical
staining of bronchial biopsies revealed co-localization of 15-LO-1 and GST
P1-1 in airway epithelial cells.

These results indicate that respiratory
infection and cell injury may activate the 15-LO pathway
 in airway epithelial cells. Furthermore, we also demonstrate that airway
epithelial cells have the capacity to produce EXC4.

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