A synthesized heterocyclic chalcone inhibits neutrophilic inflammation through K⁺‐dependent pH regulation

Abstract

Human neutrophils have a vital role in host defense and inflammatory responses in innate immune systems. Growing evidence shows that the overproduction of reactive oxygen species and granular proteolytic enzymes from activated neutrophils is linked to the pathogenesis of acute inflammatory diseases. However, adequate therapeutic targets are still lacking to regulate neutrophil functions. Herein, we report that MVBR-28, synthesized from the Mannich bases of heterocyclic chalcone, has antineutrophilic inflammatory effects through regulation of intracellular pH. MVBR-28 modulates neutrophil functions by attenuating respiratory burst, degranulation, and migration. Conversely, MVBR-28 has no antioxidant effects and fails to alter elastase activity in cell-free systems. The anti-inflammatory effects of MVBR-28 are not seen through cAMP pathways. Significantly, MVBR-28 potently inhibits extracellular Ca 2+ influx in N-formyl-methionyl-leucyl-phenylalanine (fMLF)-and thapsigarginactivated human neutrophils. Notably, MVBR-28 attenuates fMLF-induced intracellular alkalization in a K + -dependent manner, which is upstream of Ca 2+ pathways. |

Targeting formyl peptide receptor 1 with anteiso‐C13‐surfactin for neutrophil‐dominant acute respiratory distress syndrome

“…IRB‐approved informed consent was obtained from each donor. Human neutrophils were isolated from venous whole blood collected from healthy, de‐identified, volunteers, as previously described (Yang et al, 2020). Briefly, neutrophils were separated by dextran sedimentation, layered on a Ficoll–Hypaque density gradient, and centrifuged.…”