Glutamate potentiates lipopolysaccharide-stimulated interleukin-10 release from neonatal rat spinal cord astrocytes.
Interleukin-10 (IL-10) has important anti-inflammatory effects and can be protective in inflammatory conditions, such as chronic pain and infection. Exploring factors that modulate IL-10 levels may provide insight into pathomechanisms of inflammatory conditions and may provide a method of neuroprotection during these conditions. Lipopolysaccharide (LPS) stimulation of astrocytes is a source of IL-10; hence, it is of interest to investigate factors that modulate this process. Glutamate is present in increased concentrations in inflammatory conditions, and astrocytes also express glutamate receptors. The present study, therefore, investigated whether glutamate modulates LPS stimulation of IL-10 release from neonatal spinal cord astrocytes. Enzyme-linked immunosorbent assays (ELISAs) were used to quantify IL-10 release from cultured neonatal spinal cord astrocytes, and reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure IL-10 mRNA expression. Glutamate (1 mM) significantly increased LPS (1 μg/ml)-stimulated IL-10 release from astrocytes by 166% and significantly upregulated IL-10 mRNA levels. Glutamate synergistically signaled through metabotropic glutamate receptor subgroups and the phospholipase C signaling pathway. Spinal cord astrocytes may, therefore, play a larger anti-inflammatory role than first thought in situations where glutamate and a high concentration of Toll-like receptor 4 (TLR4) agonists are present.
Brain and Mind Research Institute and Bosch Institute, The University of Sydney, NSW 2006, Australia.
E L
EL
Werry
G J
GJ
Liu
M D
MD
Lovelace
R
R
Nagarajah
M R
MR
Bennett
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000819:agonists / Q000494:pharmacology; D008297:Male; D009187:Myelitis / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D018698:Glutamic Acid