title: Anti-inflammatory substances can influence some glial cell types but not others.
abstract: In rat microglial enriched cultures, expressing Toll-like receptor 4, we studied cytokine release after exposure with 1 ng/ml LPS for 0.5-24 h. Dexamethasone and corticosterone exposure served as controls. We focused on whether naloxone, ouabain, and bupivacaine, all agents with reported anti-inflammatory effects on astrocytes, could affect the release of TNF-α and IL-1β in microglia. Our results show that neither ultralow (10(-12) M) nor high (10(-6) M) concentrations of these agents had demonstrable effects on cytokine release in microglia. The results indicate that anti-inflammatory substances exert specific influences on different glial cell types. Astrocytes seem to be functional targets for anti-inflammatory substances while microglia respond directly to inflammatory stimuli and are thus more sensitive to anti-inflammatory substances like corticoids. The physiological relevance might be that astrocyte dysfunction influences neuronal signalling both due to direct disturbance of astrocyte functions and in the communication within the astrocyte networks. When the signalling between astrocytes is working, then microglia produce less pro-inflammatory cytokines.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg SE 413 45, Sweden; Department of Anaesthesiology and Intensive Care Medicine, Division of Pain Management, NU-Hospitals, Trollhättan SE 461 85, Sweden. Electronic address: johan.forshammar@vgregion.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Forshammar
authors.forename: Per
authors.initials: P
authors.lastname: Jörneberg
authors.forename: Ulrika
authors.initials: U
authors.lastname: Björklund
authors.forename: Anna
authors.initials: A
authors.lastname: Westerlund
authors.forename: Christopher
authors.initials: C
authors.lastname: Lundborg
authors.forename: Björn
authors.initials: B
authors.lastname: Biber
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hansson
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D009270:Naloxone; D010042:Ouabain; D002045:Bupivacaine
keywords: Bupivacaine; IL-1β; Lipopolysaccharide; Microglia; Naloxone; Ouabain; TNF-α