Adult Human Glia, Pericytes and Meningeal Fibroblasts Respond Similarly to IFNy but Not to TGFβ1 or M-CSF

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. Interferonc (IFN gamma) increased microglial HLA expression, but contrary to data in rodents, the anti-inflammatory cytokine transforming growth factor beta 1 (TGF beta 1) did not inhibit this increase in HLA, nor did TGF beta 1 affect basal microglial HLA expression or IFN gamma-induced astrocytic HLA expression. In contrast, IFN gamma-induced and basal microglial HLA expression, but not IFN gamma-induced astrocytic HLA expression, were strongly inhibited by macrophage colony stimulating factor (M-CSF). IFN gamma also strongly induced HLA expression in pericytes and meningeal fibroblasts, which do not basally express HLA, and this induction was completely blocked by TGF beta 1, but not affected by M-CSF. In contrast, TGF beta 1 did not block the IFN gamma-induced increase in IP-10 in pericytes and meningeal fibroblasts. These results show that IFN gamma, TGF beta 1 and MCSF have species-and cell type-specific effects on human brain cells that may have implications for their roles in adult human brain inflammation.