title: Bioactive secondary metabolites of a marine Bacillus sp. inhibit superoxide generation and elastase release in human neutrophils by blocking formyl peptide receptor 1.
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.
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, Taipei 112, Taiwan. nke0615@yahoo.com.tw
authors.forename: Shun-Chin
authors.initials: SC
authors.lastname: Yang
authors.forename: Chwan-Fwu
authors.initials: CF
authors.lastname: Lin
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Chang
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kuo
authors.forename: Yin-Ting
authors.initials: YT
authors.lastname: Huang
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Chung
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
mesh_terms: D001407:Bacillus / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002474:Cell-Free System; D045424:Complex Mixtures / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D064210:Secondary Metabolism; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*
chemical_list: D045424:Complex Mixtures; D005609:Free Radicals; D010455:Peptides; D044042:Receptors, Formyl Peptide; D013481:Superoxides; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010196:Pancreatic Elastase; D002118:Calcium