Neuronal injury regulates fractalkine: relevance for HIV-1 associated dementia.
Fractalkine (FKN), a chemokine highly expressed in the central nervous system, participates in inflammatory responses operative in many brain disorders including HIV-1 associated dementia (HAD). In this report, HIV-1 progeny virions and pro-inflammatory products led to FKN production associated with neuronal injury and apoptosis. FKN was produced by neurons and astrocytes; but differentially produced by the two cell types. Laboratory tests paralleled those in infected people where cerebrospinal fluid FKN levels in HIV-1 infected cognitively impaired (n=16) patients were found to be increased when compared to infected patients without cognitive impairment (n=8, P=0.0345). These results demonstrate a possible role of FKN in HAD pathogenesis.
Laboratory of Neurotoxicology, University of Nebraska Medical Center, Omaha, NE 68198-5215, USA.
David
D
Erichsen
Alicia L
AL
Lopez
Hui
H
Peng
Douglas
D
Niemann
Clancy
C
Williams
Michael
M
Bauer
Susan
S
Morgello
Robin L
RL
Cotter
Lisa A
LA
Ryan
Anuja
A
Ghorpade
Howard E
HE
Gendelman
Jialin
J
Zheng
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005333:Fetus; D018698:Glutamic Acid / Q000633:toxicity; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000276:immunology / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology; D014764:Viral Proteins / Q000494:pharmacology; D014771:Virion / Q000502:physiology
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D018698:Glutamic Acid