TY - JOUR
T1 - TNF-α-induced chemokine production and apoptosis in human neural precursor cells
AU - Sheng, Wen S.
AU - Hu, Shuxian
AU - Ni, Hsiao T.
AU - Rowen, Tim N.
AU - Lokensgard, James R.
AU - Peterson, Phillip K.
PY - 2005/12
Y1 - 2005/12
N2 - 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 (>98% nestin- and >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.
AB - 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 (>98% nestin- and >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.
KW - CCL2
KW - CXCL10
KW - Cytokines
KW - IP-10
KW - MCP-1
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UR - http://www.scopus.com/inward/citedby.url?scp=28844469012&partnerID=8YFLogxK
U2 - 10.1189/jlb.0405221
DO - 10.1189/jlb.0405221
M3 - Article
C2 - 16314440
AN - SCOPUS:28844469012
SN - 0741-5400
VL - 78
SP - 1233
EP - 1241
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -