Bioactive Secondary Metabolites of a Marine Bacillus sp. Inhibit Superoxide Generation and Elastase Release in Human Neutrophils by Blocking Formyl Peptide Receptor 1

Molecules

Shun-Chin Yang⁴  Chwan-Fwu Lin¹  Wen-Yi Chang²  Jimmy Kuo³  Yin-Ting Huang²  Pei-Jen Chung² 

[1] Department of Cosmetic Science, and Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; E-Mail:;Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; E-Mails:;National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan; E-Mail:;Department of Anesthesiology, Taipei Veterans General Hospital, Taipei 112, Taiwan; E-Mail:

关键词: elastase;    formyl peptide receptor;    Bacillus sp.;    neutrophil;    superoxide;   

DOI  :  10.3390/molecules18066455

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.