title: Anti-inflammatory effects of secondary metabolites of marine Pseudomonas sp. in human neutrophils are through inhibiting P38 MAPK, JNK, and calcium pathways.
abstract: Activated neutrophils play a significant role in the pathogenesis of many inflammatory diseases. The metabolites of marine microorganisms are increasingly employed as sources for developing new drugs; however, very few marine drugs have been studied in human neutrophils. Herein, we showed that secondary metabolites of marine Pseudomonas sp. (N11) significantly inhibited superoxide anion generation and elastase release in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated human neutrophils, with IC50 values of 0.67±0.38 µg/ml and 0.84±0.12 µg/ml, respectively. In cell-free systems, neither superoxide anion-scavenging effect nor inhibition of elastase activity was associated with the suppressive effects of N11. N11 inhibited the phosphorylation of p38 MAP kinase and JNK, but not Erk and Akt, in FMLP-induced human neutrophils. Also, N11 dose-dependently attenuated the transient elevation of intracellular calcium concentration in activated neutrophils. In contrast, N11 failed to alter phorbol myristate acetate-induced superoxide anion generation, and the inhibitory effects of N11 were not reversed by protein kinase A inhibitor. In conclusion, the anti-inflammatory effects of N11 on superoxide anion generation and elastase release in activated human neutrophils are through inhibiting p38 MAP kinase, JNK, and calcium pathways. Our results suggest that N11 has the potential to be developed to treat neutrophil-mediated inflammatory diseases.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shun-Chin
authors.initials: SC
authors.lastname: Yang
authors.affiliation: Department of Life Science and Graduate Institute of Biotechnology, Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung, Taiwan.
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.affiliation: Department of Cosmetic Science, and Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Chwan-Fwu
authors.initials: CF
authors.lastname: Lin
authors.affiliation: National Museum of Marine Biology & Aquarium, Pingtung, Taiwan.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Medicine, College of Medicine, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D059001:Aquatic Organisms / Q000737:chemistry; D020013:Calcium Signaling; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011549:Pseudomonas / Q000737:chemistry*; D013481:Superoxides / Q000378:metabolism; D014871:Water Microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D048051:p38 Mitogen-Activated Protein Kinases; D019272:Leukocyte Elastase