Chemokine CXCL8 is a low molecular weight neutrophil chemoattractant implicated in
various neurodegenerative disorders including Alzheimer's disease and stroke. Increased expression of
CXCL8 has been reported in serum, plasma and brain of human immunodeficiency virus (HIV)-1 infected
individuals with neurocognitive impairment, indicating its role in neuroinflammation associated
with HIV-1 infection of the brain. Since chemokines are critical in eliciting immune responses in the
central nervous system (CNS), CXCL8 is of particular importance for being one of the first chemokines
described in the brain. Activation of astrocytes and microglia by HIV-1 and virus associated proteins results in production
of this chemokine in the brain microenvironment. Consequently, CXCL8 exerts its effect on target cells via Gprotein
coupled receptors CXCR1 and CXCR2. Neutrophils are the main target cells for CXCL8; however, microglia and
neurons also express CXCR1/CXCR2 and therefore are important targets for CXCL8-mediated crosstalk. The objective of
this review is to focus on CXCL8 production, signaling and regulation in neuronal and glial cells in response to HIV-1 infection.
We highlight the role of HIV-1 secreted proteins such as trans-activator of transcription, envelope glycoprotein,
negative regulatory factor and viral protein r in the regulation of CXCL8. We discuss dual role of CXCL8 in neurodegeneration
as well as neuroprotection in the CNS. Thus, targeting CXCL8 through the development of CXCR1/CXCR2-based
therapeutic strategies to either selectively agonize or antagonize receptors may be able to selectively promote neuroprotective
and anti-inflammatory outcomes, leading to significant clinical applications in many neuroinflammatory CNS diseases,
including HIV-associated neurocognitive disorders.
Keywords: Chemokines, CXCL8, CXCR1/CXCR2, HIV-1, neurodegeneration, neuroprotection.
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