Neuronal apoptosis is mediated by CXCL10 overexpression in simian human immunodeficiency virus encephalitis.
Inflammatory mediators play a crucial role in the pathophysiology of several neurodegenerative diseases including acquired immune deficiency syndrome dementia complex. In the present study we identified a link between CXCL10 overexpression in the brain and human immunodeficiency virus dementia and demonstrated the presence of the chemokine CXCL10 and its receptor, CXCR3, in the neurons in the brains of macaques with simian human immunodeficiency virus encephalitis. Using human fetal brain cultures, we showed that treatment of these cells with either SHIV89.6P or viral gp120 resulted in induction of CXCL10 in neurons. Cultured neurons treated with the chemokine developed increased membrane permeability followed by apoptosis via activation of caspase-3. We confirmed the relevance of these findings in sections of human and macaque brains with encephalopathy demonstrating that neurons expressing CXCL10 also expressed caspase-3.
Sui
Yongjun
Y
Department of Microbiology, Immunology, and Molecular Genetics, Marion Merrell Dow Laboratory of Viral Pathogenesis, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Potula
Raghava
R
Dhillon
Navneet
N
Pinson
David
D
Li
Shanping
S
Nath
Avindra
A
Anderson
Carol
C
Turchan
Jadwega
J
Kolson
Dennis
D
Narayan
Opendra
O
Buch
Shilpa
S
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis*; D004660:Encephalitis / Q000473:pathology* / Q000821:virology*; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008251:Macaca; D008264:Macrophages / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010539:Permeability; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism*
C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases