Protein kinase C-ζ is involved in the inhibition of eosinophil migration
BMC Pharmacology volume 9, Article number: A34 (2009)
The accumulation of eosinophils in lung tissue is a hallmark of asthma, and it is believed that eosinophils play a crucial pathogenic role in allergic inflammation. Therefore, eosinophils are currently considered a major therapeutic target in allergic diseases. Prostaglandin (PG) E2 exerts anti-inflammatory and broncho-protective mechanisms in asthma, but the underlying mechanisms have remained unclear. We have shown previously that PGE2 and the EP2 receptor agonist butaprost inhibit eosinophil trafficking in vitro and in vivo .
Human eosinophils were purified by negative magnetic selection from peripheral blood. Chemotaxis was determined in 48-well microBoyden chambers and migrated eosinophils were enumerated by flow cytometry.
The chemotaxis of human eosinophils towards the chemoattractant eotaxin was attenuated by PGE2 and the selective EP4 agonist ONO-AE1-329 in a concentration-dependent manner. Pretreatment of eosinophils with the adenylyl cyclase inhibitor SQ-22536, the protein kinase A inhibitor H-89 or the p38 MAP kinase inhibitor SB-202190 did not prevent the inhibitory effect of PGE2, while the phosphatidyl inositol 3-kinase (PI3K) inhibitor LY-294002, triciribine, a specific inhibitor of Akt phosphorylation, and a myristoylated pseudosubstrate of protein kinase (PK) C-ζ (mPS), partially or completely reversed the inhibitory effect of PGE2 and ONO-AE1-329 on the migration of eosinophils towards eotaxin.
Protein kinase C is an increasingly diverse family of enzymes that has been implicated in a range of cellular functions within the eosinophil. The present data show that the PI3K/Akt/PKC-ζ pathway is involved in the negative regulation of the migration of human eosinophils mediated by EP2 and EP4 receptor activation.
Sturm EM, Schratl P, Schuligoi R, Konya V, Sturm GJ, Lippe IT, Peskar BA, Heinemann A: Prostaglandin E2 inhibits eosinophil trafficking through E-prostanoid 2 receptors. J Immunol. 2008, 181: 7273-7283.
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Sturm, E.M., Parzmair, G.P., Luschnig-Schratl, P. et al. Protein kinase C-ζ is involved in the inhibition of eosinophil migration. BMC Pharmacol 9 (Suppl 2), A34 (2009). https://doi.org/10.1186/1471-2210-9-S2-A34