The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions.
Bottom Line: Consistently, administration of QC-inhibitors in inflammatory models, such as thioglycollate-induced peritonitis reduced monocyte infiltration.Current strategies targeting CCL2 are mainly based on antibodies or spiegelmers.The application of small, orally available inhibitors of glutaminyl cyclases represents an alternative therapeutic strategy to treat CCL2-driven disorders such as atherosclerosis/restenosis and fibrosis.
Affiliation: Probiodrug AG, Halle, Germany.Show MeSH
Related in: MedlinePlus
Mentions: In a first approach, primary murine glia cells were isolated and stimulated using LPS. As expected, the stimulation of the primary cells resulted in a significant increase in CCL2 within the medium. The inhibitor PQ529 decreased the concentration of pE1-CCL2 dose-dependently (Fig 4A). Thereby, the inhibitor led to a slight but significant increase of CCL2 mRNA for the doses of 0.625 and 2.5 µM (Fig 4B), however, PQ529 did not show an effect on CCL2 expression in LPS-stimulated THP-1 cells (Fig 7A of Supporting Information). Similar to treatment of the primary glia cells, PQ529 reduced pE1-CCL2 secreted from murine and human primary macrophages (Fig 6A and B of Supporting Information).