beta-Glucan attenuates TLR2- and TLR4-mediated cytokine production by microglia.
Microglia, the resident immune cells of the brain, are activated in response to any kind of CNS injury, and their activation is critical for maintaining homeostasis within the CNS. However, during inflammatory conditions, sustained microglial activation results in damage to surrounding neuronal cells. beta-Glucans are widely recognized immunomodulators, but the molecular mechanisms underlying their immunomodulatory actions have not been fully explored. We previously reported that beta-glucans activate microglia through Dectin-1 without inducing significant amount of cytokines and chemokines. Here, we show that particulate beta-glucans attenuate cytokine production in response to TLR stimulation; this inhibitory activity of beta-glucan is mediated by Dectin-1 and does not require particle internalization. At the molecular level, beta-glucan suppressed TLR-mediated NF-kappaB activation, which may be responsible for the diminished capacity of microglia to produce cytokines in response to TLR stimulation. Overall, these results suggest that beta-glucans may be used to prevent or treat excessive microglial activation during chronic inflammatory conditions.
Shah
Vaibhav B
VB
Division of Pharmacology, College of Pharmacy, The Ohio State University, 500 W 12th Avenue, Columbus, OH 43210, USA.
Williams
David L
DL
Keshvara
Lakhu
L
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology*; D000099181:Dectin-1
D016207:Cytokines; D015850:Interleukin-6; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D000099181:Dectin-1