title: Minocycline reduces prostaglandin E synthase expression and 8-isoprostane formation in LPS-activated primary rat microglia.
abstract: Minocycline is a tetracyclic antibiotic whose non-antibacterial activities, including anti-inflammatory, antinociceptive, and neuroprotective effects, have been widely studied. Thus, a better understanding of the mechanisms underlying its pleiotropic activities is important. Primary microglial cell cultures were established from cerebral cortices of 1-day neonatal Wistar rats. Minocycline (3-100 µM) or its vehicle was added to the culture media 30 min prior to 24 h incubation with lipopolysaccharide (LPS; 10 ng/mL). Cell viability after these treatments was assessed by ATP-based luminescence test. Prostaglandin (PG) E(2) and 8-iso-PGF(2α) were determined by enzyme immunoassays. Cyclooxygenase-2 and microsomal PGE(2) synthase-1 protein levels were measured by western blot analysis. First, it was shown that minocycline (30 or 100 µM) inhibits PGE(2) production in LPS-activated primary rat microglial cells. Then, by investigating targets involved in this inhibition, it was found that minocycline (3-100 µM) inhibits microsomal PGE(2) synthase-1, but not cyclooxygenase-2, expression. Additionally, minocycline (3-100 µM) inhibited the production of 8-iso-PGF(2α). This study warrants the conduction of in vivo studies to evaluate the pharmacological relevance of these findings.
authors.forename: Leandro Francisco
authors.initials: LF
authors.lastname: Silva Bastos
authors.forename: Antônio Carlos
authors.initials: AC
authors.lastname: Pinheiro de Oliveira
authors.forename: Johannes Carolus
authors.initials: JC
authors.lastname: Magnus Schlachetzki
authors.forename: Bernd L
authors.initials: BL
authors.lastname: Fiebich
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology*; D000071876:Prostaglandin-E Synthases; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008070:Lipopolysaccharides; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D008911:Minocycline; D015232:Dinoprostone