Microglia express GABA(B) receptors to modulate interleukin release.
gamma-Aminobutyric acid (GABA) can act as a neuroprotective agent besides its well-established role as the main inhibitory neurotransmitter in the CNS. Here we report that microglial cells express GABA(B) receptors indicating that these prominent immunocompetent cells in the brain are a target for GABA. Agonists of GABA(B) receptors triggered the induction of K(+) conductance in microglial cells from acute brain slices and in culture. Both subunits of GABA(B) receptors were identified in cultured microglia by Western blot analysis and immunocytochemistry, and were detected on a subpopulation of microglia in situ by immunohistochemistry. In response to facial nerve axotomy, we observed an increase in GABA(B) receptor expressing microglial cells in the facial nucleus. We activated microglial cells in culture with lipopolysaccharide (LPS) to induce the release of interleukin-6 and interleukin-12p40. This release activity was attenuated by simultaneous activation of the GABA(B) receptors indicating that GABA can modulate the microglial immune response.
Kuhn
Susanne A
SA
Department of Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine, D-13125 Berlin, Germany.
van Landeghem
Frank K H
FK
Zacharias
Robert
R
Färber
Katrin
K
Rappert
Angelika
A
Pavlovic
Sanja
S
Hoffmann
Anja
A
Nolte
Christiane
C
Kettenmann
Helmut
H
D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020220:Facial Nerve Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D005911:Gliosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D015221:Potassium Channels; D021122:Protein Subunits; D018080:Receptors, GABA-B; D018664:Interleukin-12; D005680:gamma-Aminobutyric Acid