title: Adult human glia, pericytes and meningeal fibroblasts respond similarly to IFNy but not to TGFβ1 or M-CSF.
abstract: The chemokine Interferon gamma-induced protein 10 (IP-10) and human leukocyte antigen (HLA) are widely used indicators of glial activation and neuroinflammation and are up-regulated in many brain disorders. These inflammatory mediators have been widely studied in rodent models of brain disorders, but less work has been undertaken using human brain cells. In this study we investigate the regulation of HLA and IP-10, as well as other cytokines and chemokines, in microglia, astrocytes, pericytes, and meningeal fibroblasts derived from biopsy and autopsy adult human brain, using immunocytochemistry and a Cytometric Bead Array. Interferonγ (IFNγ) increased microglial HLA expression, but contrary to data in rodents, the anti-inflammatory cytokine transforming growth factor β1 (TGFβ1) did not inhibit this increase in HLA, nor did TGFβ1 affect basal microglial HLA expression or IFNγ-induced astrocytic HLA expression. In contrast, IFNγ-induced and basal microglial HLA expression, but not IFNγ-induced astrocytic HLA expression, were strongly inhibited by macrophage colony stimulating factor (M-CSF). IFNγ also strongly induced HLA expression in pericytes and meningeal fibroblasts, which do not basally express HLA, and this induction was completely blocked by TGFβ1, but not affected by M-CSF. In contrast, TGFβ1 did not block the IFNγ-induced increase in IP-10 in pericytes and meningeal fibroblasts. These results show that IFNγ, TGFβ1 and M-CSF have species- and cell type-specific effects on human brain cells that may have implications for their roles in adult human brain inflammation.
authors: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand ; Gravida - National Research Centre for Growth and Development, Auckland, New Zealand ; Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
authors: Amy M
authors: AM
authors: Smith
authors: E Scott
authors: ES
authors: Graham
authors: Sheryl Xia
authors: SX
authors: Feng
authors: Robyn L
authors: RL
authors: Oldfield
authors: Peter M
authors: PM
authors: Bergin
authors: Edward W
authors: EW
authors: Mee
authors: Richard L M
authors: RL
authors: Faull
authors: Maurice A
authors: MA
authors: Curtis
authors: Mike
authors: M
authors: Dragunow
mesh_terms: D000328:Adult; D001253:Astrocytes / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006681:HLA-D Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008578:Meninges / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology*; D020286:Pericytes / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D018925:Chemokines; D006681:HLA-D Antigens; D053773:Transforming Growth Factor beta1; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma