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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-3-3
pubmed:abstractText
Human neuroblastoma SK-N-SH cells strongly express CXC-chemokine receptor 4 (CXCR4), the principal coreceptor for X4 HIV-1 strains, and its natural ligand stromal cell-derived factor 1 (SDF-1, recently renamed CXCL12). We investigated the impact of CXCR4 blockade by the specific CXCR4 antagonist AMD3100 or by X4 HIV-1 virus particles on the growth and survival of neuroblastoma SK-N-SH cells. SK-N-SH cell proliferation was inhibited byAMD3100 and anti-CXCL12 neutralizing antibodies, but enhanced by exogenously added CXCL12. Upon prolongedexposure to AMD3100, SK-N-SH cell death occurred throughdeficit of survival-promoting and growth-stimulatory signals generated by endogenous CXCL12. In analogy with the observations made with the CXCR4 inhibitor AMD3100, the X4 HIV-1 strains IIIB and SF-2, but not the R5 strain BaL, caused a marked cytopathic effect and strongly effected SK-N-SH cell death after at least 10 days of incubation. However, no virus production could be detected in the HIV-1-inoculated SK-N-SH cell cultures. Exogenously added CXCL12 afforded partial protection against X4 HIV-1-induced cytopathicity in SK-N-SH cells. Our data indicate that the endogenous CXCL12/CXCR4 signaling axis is critical for neuroblastoma cell survival and proliferation. Long-term blockade of CXCR4 through physical contact with the X4 HIV-1 envelope can cause neuronal cell death. This mechanism may possibly play a role in X4 HIV-associated neurodegeneration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0145-5680
pubmed:author
pubmed:issnType
Print
pubmed:volume
49 Online Pub
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
OL443-52
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
X4 HIV-1 induces neuroblastoma cell death by interference with CXCL12/CXCR4 interaction.
pubmed:affiliation
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Sigrid.hatse@rega.kuleuven.ac.be
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't