In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 78, No. 6 ( 2005-12-01), p. 1233-1241
Kurzfassung:
Recent studies have shown that proinflammatory cytokines damage rodent neural precursor cells (NPCs), a source of self-renewing, multipotent cells that play an important role in the developing as well as adult brain. In this study, the effects of tumor necrosis factor α (TNF-α) on cytokine and chemokine production by human NPCs ( & gt;98% nestin- and & gt;90% A2B5-positive), obtained from 6- to 8-week-old fetal brain specimens, were evaluated. NPCs stimulated with this proinflammatory cytokine were found to produce abundant amounts of the chemokines monocyte chemoattractant protein 1 (MCP-1)/CC chemokine ligand 2 (CCL2) and interferon-inducible protein 10 (IP-10)/CXC chemokine ligand 10 (CXCL10) in a time- and concentration-dependent manner. TNF-α treatment also induced NPC apoptosis. Receptors for TNF [TNFRI (p55) and TNFRII (p75)] mRNA were constitutively expressed on NPCs. However, only TNFRI was involved in TNF-α-induced chemokine production and apoptosis by NPCs, as anti-TNFRI but not anti-TNFRII antibodies blocked the stimulatory effect. TNF-α treatment induced p38 mitogen-activated protein kinase (MAPK) phosphorylation in NPCs, and SB202190, an inhibitor of p38 MAPK, blocked TNF-α-induced chemokine production. Thus, this study demonstrated that NPCs constitutively express receptors for TNF-α, which when activated, trigger via a p38 MAPK signaling pathway production of two chemokines, MCP-1/CCL2 and IP-10/CXCL10, which are involved in infectious and inflammatory diseases of the brain.
Materialart:
Online-Ressource
ISSN:
0741-5400
,
1938-3673
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2005
ZDB Id:
2026833-6
SSG:
12
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