title: Classical and Alternative Activation of Cyanobacterium Oscillatoria sp. Lipopolysaccharide-Treated Rat Microglia in vitro.
abstract: The purpose of this investigation was to test the hypothesis that an in vitro exposure to cyanobacterium Oscillatoria sp. Lipopolysaccharide (LPS) might result in classical and alternative activation of rat neonatal microglia. Using Escherichia coli LPS-primed microglia as a positive control, this study revealed that treatment of rat microglia with Oscillatoria sp. LPS for 17 h in vitro resulted in both classical and alternative activation as well as concomitant pro-inflammatory and anti-inflammatory mediator release, in a concentration-dependent manner: (1) treatment with 0.1-10 000 ng/ml Oscillatoria sp. LPS resulted in minimal lactic dehydrogenase (LDH) release, induced concentration-dependent and statistically significant O2 (-) generation, matrix metalloproteinase-9 (MMP-9) release, generation of the cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the chemokines macrophage inflammatory protein-2 (MIP-2/CXCL2), interferon γ-induced protein 10 kDa (IP-10/CXCL-10), (MIP-1α/CCL3), monocyte chemotactic protein-1 (MCP-1/CCL2), regulated on activation, normal T cell expressed and secreted (RANTES/CCL5), and the alternative activation cytokine IL-10; (3) in contrast, treatment with 100 000 ng/ml Oscillatoria sp. LPS appeared to damage the microglia cell membrane, because it resulted in minimal O2 (-) generation, statistically significant LDH release, and a decrease in the generation of all the cytokines and chemokines investigated, with the exception of IL-1α and cytokine-induced neutrophil chemoattractant 1 (CINC-1/CXCL1) generation, which was increased. Thus, our results provide experimental support for our working hypothesis, namely that Oscillatoria sp. LPS induces classical and alternative activation of rat brain microglia in vitro in a concentration-dependent manner, namely 0.1-10 000 ng/ml Oscillatoria sp. LPS, when microglia cells were shown to be viable. Furthermore, should cyanobacterium Oscillatoria sp. LPS gain entry into the CNS, our findings suggest that classical and alternative activation of rat brain microglia in vivo, might lead to concomitant mediator release that could result in an interplay between neuroinflammation and neural repair in a concentration-dependent manner.
authors.affiliation: *Department of Pharmacology, Chicago College of Osteopathic Medicine and amayer@midwestern.edu.
authors.forename: Alejandro M S
authors.initials: AM
authors.lastname: Mayer
authors.affiliation: Biomedical Sciences Program, College of Health Sciences, Midwestern University, Downers Grove, Illinois 60515; and.
authors.forename: Joseph
authors.initials: J
authors.lastname: Murphy
authors.affiliation: Biomedical Sciences Program, College of Health Sciences, Midwestern University, Downers Grove, Illinois 60515; and.
authors.forename: David
authors.initials: D
authors.lastname: MacAdam
authors.affiliation: Biomedical Sciences Program, College of Health Sciences, Midwestern University, Downers Grove, Illinois 60515; and.
authors.forename: Christopher
authors.initials: C
authors.lastname: Osterbauer
authors.affiliation: Biomedical Sciences Program, College of Health Sciences, Midwestern University, Downers Grove, Illinois 60515; and.
authors.forename: Imaan
authors.initials: I
authors.lastname: Baseer
authors.affiliation: *Department of Pharmacology, Chicago College of Osteopathic Medicine and.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Hall
authors.affiliation: Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96882.
authors.forename: Domonkos
authors.initials: D
authors.lastname: Feher
authors.affiliation: Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96882.
authors.forename: Phillip
authors.initials: P
authors.lastname: Williams
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D054300:Oscillatoria / Q000472:pathogenicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D013481:Superoxides; D013929:Thromboxane B2; D007770:L-Lactate Dehydrogenase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Oscillatoria; alternative activation; classical activation; cyanobacteria; lipopolysaccharide; microglia; rat