Differential regulation of microglial keratan sulfate immunoreactivity by proinflammatory cytokines and colony-stimulating factors.

Abstract:

: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-alpha (TNF-alpha). By contrast, the Th1 cytokine interferon-gamma (IFN-gamma) downregulated KS-IR, both when applied alone or in combination with either GM-CSF, M-CSF, or TNF-alpha. In vivo, the intracerebroventricular administration of IFN-gamma, but not TNF-alpha, 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-gamma and represent the first evidence of cytokine-dependent proteoglycan regulation in the CNS.

journal_name

Glia

journal_title

Glia

authors

Jander S,Schroeter M,Fischer J,Stoll G

doi

10.1002/(sici)1098-1136(200006)30:4<401::aid-glia9

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

401-10

issue

4

eissn

0894-1491

issn

1098-1136

pii

10.1002/(SICI)1098-1136(200006)30:4<401::AID-GLIA9

journal_volume

30

pub_type

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