Role of activated astrocytes in neuronal damage: potential links to HIV-1-associated dementia.
HIV-1-associated dementia (HAD) is an important complication of HIV-1 infection. Reactive astrogliosis is a key pathological feature in HAD brains and in other central nervous system (CNS) diseases. Activated astroglia may play a critical role in CNS inflammatory diseases such as HAD. In order to test the hypothesis that activated astrocytes cause neuronal injury, we stimulated primary human fetal astrocytes with HAD-relevant pro-inflammatory cytokine IL-1beta. IL-1beta-activated astrocytes induced apoptosis and significant changes in metabolic activity in primary human neurons. An FITC-conjugated pan-caspase inhibitor peptide FITC-VAD-FMK was used for confirming caspase activation in neurons. IL-1beta activation enhanced the expression of death protein FasL in astrocytes, suggesting that FasL is one of the potential factors responsible for neurotoxicity observed in HAD and other CNS diseases involving glial inflammation. Our data presented here add to the developing picture of role of activated glia in HAD pathogenesis.
Deshpande
M
M
Laboratories of Cellular Neuroimmunology and Neurotoxicology, Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA.
Zheng
J
J
Borgmann
K
K
Persidsky
R
R
Wu
L
L
Schellpeper
C
C
Ghorpade
A
A
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D053222:Fas Ligand Protein; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D007375:Interleukin-1 / Q000494:pharmacology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017077:Culture Media, Conditioned; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D007375:Interleukin-1; D007381:Intermediate Filament Proteins; C489788:MAP2 protein, human; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D016900:Neurofilament Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; C007293:DAPI; D020169:Caspases; C022616:thiazolyl blue