Chemokines released from astroglia by vasoactive intestinal peptide. Mechanism of neuroprotection from HIV envelope protein toxicity.
The mechanism through which VIP prevents neurotoxicity associated with HIV envelope protein has been shown to involve the release of a beta-chemokine, MIP-1 alpha. Astrocytes stimulated with subnanomolar concentrations of VIP caused the release of MIP-1 alpha and RANTES, both of which have been shown to prevent neuronal cell death associated with gp120. It is further proposed that gp120 causes neuronal cell death, in part, by competing with endogenous chemokines at various chemokines receptors in the brain that are necessary for neuronal survival. Although the chemokines are known to be mediators of inflammation, our studies suggest that these compounds have additional roles as neuroprotective agents that depend on the concentration of chemokine, cellular microenvironment, and stage of development of target neurons. Our studies further imply that in a developing system, stimulation with a MIP-1 alpha like substance is necessary for neuronal survival and interference with this action results in neuronal cell death.
Brenneman
D E
DE
Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20892, USA. dbrenn@codon.nih.gov
Hauser
J
J
Spong
C Y
CY
Phillips
T M
TM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000502:physiology; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009500:Neutralization Tests; D051381:Rats; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D000906:Antibodies; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D015699:HIV Envelope Protein gp120; D019402:Macrophage Inflammatory Proteins; D018696:Neuroprotective Agents; D014660:Vasoactive Intestinal Peptide