TY - JOUR
T1 - Altered apolipoprotein E secretion in cytokine treated human astrocyte cultures
AU - Baskin, Fred
AU - Smith, George M.
AU - Fosmire, Jennifer A.
AU - Rosenberg, Roger N.
N1 - Funding Information:
We thank Drs W.E. Wright and M.D. West for providing the initial primary human astrocytes, and the laboratory of Dr K. Wynn for the ApoE genotyping. This work was supported by an Alzheimer's Disease Center NIH NIA Grant P-30 AG-30-12300 and by funds donated by M.B. `Duke' Rudman for the Josephine Rudman Laboratory for Alzheimer's Disease Research.
PY - 1997/5/1
Y1 - 1997/5/1
N2 - Apolipoprotein E (ApoE), postulated to be a major lipid carrier protein in brain, is synthesized and secreted primarily by astrocytes and is involved in brain development and repair. We have analyzed its secretion in primary cultures of older (high passage) slowly dividing and younger (lower passage) rapidly dividing fetal human astrocytes exposed to various inflammatory and anti-inflammatory cytokines, alone and in combination. ApoE secretion was reduced in high passage astrocytes when compared to lower passage astrocytes. A further reduction in ApoE secretion in high passage cells was consistently produced by the combination of cytokines interleukin 1 (IL-1) alpha and beta and interferon (IFN-gamma) cytokines or by the basic fibroblast growth factor (basic-FGF) alone. Epidermal growth factor (EGF) increased ApoE secretion. The combination of these cytokine effects in chronically degenerating brain regions of Alzheimer's disease and other neurodegenerative diseases could reduce the amount of ApoE available for neuronal regeneration. EGF, or agents inducing EGF, could ameliorate these ApoE deficiencies.
AB - Apolipoprotein E (ApoE), postulated to be a major lipid carrier protein in brain, is synthesized and secreted primarily by astrocytes and is involved in brain development and repair. We have analyzed its secretion in primary cultures of older (high passage) slowly dividing and younger (lower passage) rapidly dividing fetal human astrocytes exposed to various inflammatory and anti-inflammatory cytokines, alone and in combination. ApoE secretion was reduced in high passage astrocytes when compared to lower passage astrocytes. A further reduction in ApoE secretion in high passage cells was consistently produced by the combination of cytokines interleukin 1 (IL-1) alpha and beta and interferon (IFN-gamma) cytokines or by the basic fibroblast growth factor (basic-FGF) alone. Epidermal growth factor (EGF) increased ApoE secretion. The combination of these cytokine effects in chronically degenerating brain regions of Alzheimer's disease and other neurodegenerative diseases could reduce the amount of ApoE available for neuronal regeneration. EGF, or agents inducing EGF, could ameliorate these ApoE deficiencies.
KW - Alzheimer's disease (AD)
KW - apolipoprotein E (ApoE)
KW - astrocyte
KW - basic-fibroblast growth factor (basic-FGF)
KW - epidermal growth factor (EGF)
KW - interferon-gamma (IFN-gamma)
KW - interleukin-1 (IL-1)
KW - secretion
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U2 - 10.1016/S0022-510X(96)05335-X
DO - 10.1016/S0022-510X(96)05335-X
M3 - Article
C2 - 9125385
AN - SCOPUS:0031149081
SN - 0022-510X
VL - 148
SP - 15
EP - 18
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1
ER -