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
• 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.