Brain activation of monocyte-lineage cells: involvement of interleukin-6.
Immune processes such as phagocytosis of debris and antigen presentation can be damaging to the function and survival of brain cells. Understanding what conditions and factors mediate immune processes in the brain is central to ameliorating the pathology associated with brain injury and disease. The elevation of secreted interleukin (IL)-6 is a common feature of brain injury and neurodegenerative pathology. Using organotypic brain slice coculture, the effects of brain-derived soluble factors on immune functions in the BV2 microglial cell line were studied. We have previously shown that brain-derived soluble factors upregulated phagocytic activity and class II major histocompatibility complex (MHC II) expression and altered BV2 morphology in a manner selective for microglia and not peripheral macrophages. The present study used IL-6-neutralizing antibody to show that brain-derived IL-6 was at least partially responsible for the brain coculture-induced upregulation of MHC II expression in the BV2 microglia. Additionally, IL-6 upregulated phagocytic activity and induced morphological changes in the BV2 cells similar to brain coculture. These effects were selective for microglia, as they were not observed in peripheral macrophage cell types. The ability of IL-6-neutralizing antibody to downregulate MHC II expression while maintaining enhanced phagocytic activity could potentially evade an antagonizing immune response associated with brain injury or disease.
Shafer
Lisa L
LL
Department of Cell Biology Neurobiology and Anatomy, Loyola University of Chicago Medical Center, Maywood, Ill., USA.
McNulty
John A
JA
Young
M Rita I
MR
D000818:Animals; D001930:Brain Injuries / Q000276:immunology / Q000503:physiopathology; D019070:Cell Lineage / Q000276:immunology; D048430:Cell Shape / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005911:Gliosis / Q000276:immunology* / Q000503:physiopathology; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D009924:Organ Culture Techniques; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6