HCH6-1 is a competitive antagonist of Formyl peptide receptor 1 (FPR1) and may have potential as a new therapeutic agent for treating FPR1-involved inflammatory lung diseases.
During the inflammatory process, neutrophils are recruited into inflammatory areas to eliminate invasive pathogens. Formyl peptide receptor 1 (FPR1) typically facilitates neutrophil immune responses in the presence of N-formyl peptides derived from bacteria in vitro. HCH6-1, a competitive dipeptide antagonist of FPR1, shows a potent inhibitory effect on FPR1-agonist-activated human neutrophils. HCH6-1 significantly inhibited superoxide anion generation in fMLF (FPR1 agonist)-activated neutrophils, with IC50 of 0.32 ± 0.03 μM. Further, HCH6-1 significantly inhibited elastase release in fMLF-activated neutrophils, with IC50 of 0.57 ± 0.07 μM. HCH6-1 dose dependently diminished CD11b expression up-regulated by fMLF in human neutrophils. Furthermore, HCH6-1 reduced the neutrophil migration induced by fMLF suggesting that HCH6-1 impaired chemotaxis only in FPR1-activated neutrophils. Compared with the controls, in treated neutrophils, HCH6-1 dose-dependently inhibited the binding of FNLFNYK to FPR1. The protective effect of HCH6-1 in LPS (lipopolysaccharide)-induced ALI (acute lung injury) was tested in vivo. HCH6-1 pretreatment reduced inflammatory cell infiltration and distortion of pulmonary architecture in the presence of LPS[1].
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