Horiuchi Lab. Devertment of molecular and cellular biology, Institute of develoment, aging, and cancer, Tohoku university

The relationship between PGE2 and netosis

"Upon stimulation, neutrophils release their nuclear contents called neutrophil extracellular traps (NETs), which contain unfolded chromatin and lysosomal enzymes. NETs have been demonstrated to play a critical role in host defence, although the role of PGE2, a bioactive substance generated in inflammatory tissues, in the formation of NETs remains unclear.The effects of PGE2, agonists and antagonists of its receptors, andmodulators of the cAMP–PKA pathway on the formation of NETswere examined in vitro in isolated neutrophils and in vivo in a newly established mouse model.PGE2 inhibited PMA-induced NET formation in vitro through EP2 and EP4 Gαs-coupled receptors. Incubation with a cell-permeablecAMP analogue, dibutyryl cAMP, or various inhibitors of a cAMP-degrading enzyme, PDE, also suppressed NET formation. In the assay established here, where an agarose gel was s.c. implanted inmice and NET formation was detected on the surface of the gel, the extent of the NET formed was inhibited in agarose gels containing rolipram, a PDE4 inhibitor, and butaprost, an EP2 receptor agonist. PGE2 inhibits NET formation through the production of cAMP. These findings will contribute to the development of novel treatments for NETosis-related diseases." (Shishikura et al, Br J Pharm, 2015)