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Differential regulation of microglial keratan sulfate immunoreactivity by proinflammatory cytokines and colony‐stimulating factors
Author(s) -
Jander Sebastian,
Schroeter Michael,
Fischer Johannes,
Stoll Guido
Publication year - 2000
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(200006)30:4<401::aid-glia90>3.0.co;2-6
Subject(s) - microglia , cytokine , biology , tumor necrosis factor alpha , proinflammatory cytokine , granulocyte macrophage colony stimulating factor , immunology , interferon gamma , macrophage , inflammation , macrophage inflammatory protein , keratan sulfate , neuroglia , proteoglycan , microbiology and biotechnology , central nervous system , in vitro , endocrinology , interleukin , biochemistry , extracellular matrix
Resident microglia of the rat CNS express a unique type of keratan sulfate immunoreactivity (KS‐IR) that is lacking on peripheral monocytes/macrophages and associated with a so far unknown proteoglycan core protein. Microglial KS‐IR is downregulated during T‐cell‐mediated autoimmune inflammation but largely preserved in degenerative lesion paradigms. This study addresses the role of cytokines and colony‐stimulating factors in the regulation of microglial KS‐IR. In vitro, ramified microglia in coculture with astrocytes, but not isolated microglia, constitutively expressed KS‐IR under control conditions. In both culture paradigms, KS‐IR was increased significantly by macrophage‐ (M‐CSF) and granulocyte/macrophage colony‐stimulating factors (GM‐CSF), as well as tumor necrosis factor‐α (TNF‐α). By contrast, the Th1 cytokine interferon‐γ (IFN‐γ) downregulated KS‐IR, both when applied alone or in combination with either GM‐CSF, M‐CSF, or TNF‐α. In vivo, the intracerebroventricular administration of IFN‐γ, but not TNF‐α, to healthy rats led to an almost complete disappearance of KS‐IR from ramified brain microglia. Our data suggest that the expression of microglial KS‐IR is under dominant negative control by the Th1 cell cytokine IFN‐γ and represent the first evidence of cytokine‐dependent proteoglycan regulation in the CNS. GLIA 30:401–410, 2000. © 2000 Wiley‐Liss, Inc.