Abstract
It is well known that overwhelming neutrophil activation is closely related to acute and chronic inflammatory injuries. Formyl peptide receptor 1 (FPR1) plays an important role in activation of neutrophils and may represent a potent therapeutic target in inflammatory diseases. In the present study, we demonstrated that IA-LBI07-1 (IA), an extract of bioactive secondary metabolites from a marine Bacillus sp., has anti-inflammatory effects in human neutrophils. IA significantly inhibited superoxide generation and elastase release in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated neutrophils, but failed to suppress the cell responses activated by non-FPR1 agonists. IA did not alter superoxide production and elastase activity in cell-free systems. IA also attenuated the downstream signaling from FPR1, such as the Ca2+, MAP kinases and AKT pathways. In addition, IA inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analogue of FMLP, to FPR1 in human neutrophils and FPR1-transfected HEK293 cells. Taken together, these results show that the anti-inflammatory effects of IA in human neutrophils are through the inhibition of FPR1. Also, our data suggest that IA may have therapeutic potential to decrease tissue damage induced by human neutrophils.
Highlights
Neutrophils play an important role in host defense systems against pathogen invasion and to clear damaged tissues [1]
We showed that IA, an extract of bioactive secondary metabolites from a marine Bacillus sp., exerted anti-inflammatory effects
These results demonstrated that IA inhibited respiratory burst and degranulation in FMLP-activated neutrophils
Summary
Neutrophils play an important role in host defense systems against pathogen invasion and to clear damaged tissues [1]. The attenuation of neutrophil activation is a critical step to treat inflammatory diseases. Previous studies demonstrated that activation of FPR1 on neutrophils induces severe inflammatory response syndrome and organ damage [8,9]. Concerns have been suggested that the pharmacologic potential of FPR1 as a therapeutic target for the development of new drugs to treat inflammatory diseases [10]. A number of secondary metabolites from marine organisms have been shown to display potential pharmacological activities, such as anti-inflammatory, bactericidal, and antiviral effects [12,13]. Our data suggest that IA-LBI07-1 (IA), an extract of bioactive secondary metabolites from a marine Bacillus sp., inhibits superoxide generation and elastase release in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated human neutrophils through binding to FPR1
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