Regulation of microglial activation by TGF-beta, IL-10, and CSF-1.
Microglia are the resident macrophages of the brain and as such are active participants in immune responses in the central nervous system. Normal resting microglia express low levels of MHC class I and class II antigens and do not produce proinflammatory cytokines. However, microglial immune functions are induced in areas of infection or injury. To understand regulation of cytokines that are secreted by and act upon microglia, we examined production of interleukin (IL) -12, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) by lipopolysaccharide (LPS)-stimulated microglia. We observed secretion of IL-12, TNF-alpha, and NO following stimulation of microglia with LPS. Addition of IL-10 suppressed TNF-alpha, IL-12, and NO production. Transforming growth factor-beta (TGF-beta) also inhibited TNF-alpha and NO but did not affect IL-12 secretion. IL-12 secretion became sensitive to TGF-beta inhibition when microglia were cultured in the absence of CSF-1. In addition to its effect on the response to TGF-beta, CSF-1 suppressed the response of microglia to LPS. These data suggest that CSF-1 may contribute to the immunologically privileged status of the central nervous system.
Lodge
P A
PA
Department of Neurology, Vanderbilt University Medical School, Nashville, Tennessee, USA.
Sriram
S
S
D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000032:analysis; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D016173:Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens