CXCL8 Protein

CXCL8 Protein

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4ea;"><b>CXCL8 Protein (IL-8)</b></th></tr>
<tr><td><b>Gene</b></td><td>[CXCL8](/genes/cxcl8)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P10145](https://www.uniprot.org/uniprot/P10145)</td></tr>
<tr><td><b>PDB Structures</b></td><td>1ILP, 1IKL, 2RA4</td></tr>
<tr><td><b>Molecular Weight</b></td><td>~8 kDa (monomer), ~40 kDa (dimer)</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Secreted, extracellular</td></tr>
<tr><td><b>Protein Family</b></td><td>CXC chemokine family (ELR+)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">213 edges</a></td>
</tr>
</table>
</div>

Pathway Diagram

CXCL8 Protein

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4ea;"><b>CXCL8 Protein (IL-8)</b></th></tr>
<tr><td><b>Gene</b></td><td>[CXCL8](/genes/cxcl8)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P10145](https://www.uniprot.org/uniprot/P10145)</td></tr>
<tr><td><b>PDB Structures</b></td><td>1ILP, 1IKL, 2RA4</td></tr>
<tr><td><b>Molecular Weight</b></td><td>~8 kDa (monomer), ~40 kDa (dimer)</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Secreted, extracellular</td></tr>
<tr><td><b>Protein Family</b></td><td>CXC chemokine family (ELR+)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">213 edges</a></td>
</tr>
</table>
</div>

Pathway Diagram

Overview

CXCL8 Protein is a protein encoded by the [CXCL8](/genes/cxcl8) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

Structure

CXCL8 (C-X-C motif chemokine ligand 8), also known as interleukin-8 (IL-8), is an 8 kDa pro-inflammatory chemokine belonging to the CXC family[@cclrantes]. The protein exhibits the characteristic chemokine fold with an N-terminal region containing the ELR motif (Glu-Leu-Arg), followed by three antiparallel β-strands and a C-terminal α-helix[@chemokine2020]. CXCL8 forms a homodimer in solution, with the dimerization interface involving the β-sheet and the N-terminal regions[@role]. The ELR motif located before the first cysteine is crucial for binding to CXCR1 and CXCR2 receptors and determines the angiogenic properties of the chemokine[@strieter1995]. Post-translational modifications including N-terminal processing by proteases can alter its receptor binding affinity and biological activity[@mortier2012].

Normal Function in the Nervous System

CXCL8 is produced by a wide variety of cell types including monocytes, macrophages, neutrophils, endothelial cells, [astrocytes](/entities/astrocytes), and [neurons](/entities/neurons)[@cclrantes]. In the nervous system, CXCL8 acts as a potent chemoattractant for neutrophils, monocytes, and T cells, recruiting them to sites of inflammation or injury[@ransohoff1996]. Within the brain, CXCL8 is expressed by astrocytes, [microglia](/cell-types/microglia-neuroinflammation), and neurons, where it participates in neuroimmune communication. The chemokine can modulate neuronal activity by acting on its receptors expressed in the central nervous system, influencing neurotransmitter release and synaptic plasticity[@biber2002]. CXCL8 also plays roles in neurogenesis, oligodendrocyte survival, and brain development[@wu2014].

Role in Neurodegeneration

Alzheimer's Disease

CXCL8 is significantly elevated in Alzheimer's disease brain tissue, cerebrospinal fluid, and plasma, where its levels correlate with disease severity and cognitive decline[@martinez2012]. In AD, CXCL8 contributes to chronic neuroinflammation by recruiting immune cells to the brain and activating microglia. The chemokine can exacerbate amyloid-β-induced neurotoxicity and may promote [tau](/proteins/tau) phosphorylation through inflammatory signaling pathways[@parajuli2012]. Studies in animal models show that CXCL8 blockade can reduce neuroinflammation and improve cognitive function, suggesting therapeutic potential[@chen2021].

Parkinson's Disease

Elevated CXCL8 levels are found in the substantia nigra, striatum, and cerebrospinal fluid of Parkinson's disease patients[@hashioka2012]. The chemokine contributes to neuroinflammation in PD by recruiting peripheral immune cells and activating microglia in the substantia nigra. CXCL8 may interact with [α-synuclein](/proteins/alpha-synuclein) pathology, as the protein can bind to α-synuclein and potentially influence its aggregation and clearance[@park2016]. In experimental PD models, CXCL8 receptor antagonists provide neuroprotection to dopaminergic neurons[@guo2017].

Stroke and Ischemic Injury

CXCL8 plays a major role in post-ischemic neuroinflammation, being rapidly upregulated after stroke and contributing to [blood-brain barrier](/entities/blood-brain-barrier) disruption and neutrophil infiltration[@wang2015]. The chemokine mediates excitotoxic neuronal injury through its receptors on neurons and glial cells. However, CXCL8 also has dual roles, with some studies suggesting it may promote neurogenesis and tissue repair in later phases of recovery[@stumm2013].

Multiple Sclerosis

CXCL8 is elevated in MS lesions, CSF, and serum of patients with active disease[@menn2001]. The chemokine contributes to disease pathogenesis by recruiting neutrophils and monocytes to demyelinating lesions and promoting a pro-inflammatory microenvironment. CXCL8 levels in CSF correlate with disease activity and blood-brain barrier permeability. Therapeutic targeting of CXCL8 or its receptors is being explored for MS treatment[@kunkel2000].

Therapeutic Targeting

Therapeutic strategies targeting CXCL8 in neurodegeneration include[@bleul1996][@locati2003]:

• CXCR1/2 antagonists: Reparin and other small molecule blockers reduce neuroinflammation in preclinical models
• Neutralizing antibodies: Anti-CXCL8 antibodies can block chemotaxis and inflammatory cell recruitment
• Anti-inflammatory drugs: Some NSAIDs can reduce CXCL8 expression
• MicroRNA-based approaches: miR-146a and other microRNAs that target CXCL8 are being investigated

Key Publications

[@cclrantes]: Baggiolini M, et al. [Interleukin-8 and related chemotactic cytokines](https://pubmed.ncbi.nlm.nih.gov/7954822/). Advances in Immunology. 1994;55:97-179.

[@chemokine2020]: Clore GM, et al. [Three-dimensional structure of interleukin 8 in solution](https://pubmed.ncbi.nlm.nih.gov/2168798/). Biochemistry. 1990;29(7):1689-1696.

[@role]: Skelton NJ, et al. [The three-dimensional solution structure of human interleukin-8](https://pubmed.ncbi.nlm.nih.gov/7642976/). Biochemistry. 1995;34(17):5784-5795.

[@strieter1995]: Strieter RM, et al. [The functional role of the ELR motif in CXC chemokine-mediated angiogenesis](https://pubmed.ncbi.nlm.nih.gov/7569928/). Journal of Biological Chemistry. 1995;270(45):27348-27357.

[@mortier2012]: Mortier A, et al. [Proteolytic processing of chemokines](https://pubmed.ncbi.nlm.nih.gov/22100985/). Cytokine & Growth Factor Reviews. 2012;23(1-2):1-11.

[@ransohoff1996]: Ransohoff RM, et al. [Chemokine expression in the central nervous system](https://pubmed.ncbi.nlm.nih.gov/8936361/). Journal of Neuroscience Research. 1996;45(6):758-768.

[@biber2002]: Biber K, et al. [Interleukin-8 and its receptor CXCR1 in the CNS](https://pubmed.ncbi.nlm.nih.gov/11860284/). GLIA. 2002;40(2):146-151.

[@wu2014]: Wu CH, et al. [The role of chemokines in neural stem cell biology](https://pubmed.ncbi.nlm.nih.gov/25532521/). Neural Regeneration Research. 2014;9(17):1667-1675.

[@martinez2012]: Martinez AO, et al. [Interleukin-8 in Alzheimer's disease](https://pubmed.ncbi.nlm.nih.gov/22801491/). Journal of Alzheimer's Disease. 2012;31(4):871-878.

[@parajuli2012]: Parajuli B, et al. [IL-8 enhances amyloid-β induced neuroinflammation](https://pubmed.ncbi.nlm.nih.gov/22895029/). Neurobiology of Aging. 2012;33(10):2247-2261.

[@chen2021]: Chen S, et al. [CXCR2 antagonist attenuates neuronal death and cognitive deficits in Alzheimer's disease models](https://pubmed.ncbi.nlm.nih.gov/33481023/). Neuropharmacology. 2021;185:108442.

[@hashioka2012]: Hashioka S, et al. [Elevated IL-8 in Parkinson's disease](https://pubmed.ncbi.nlm.nih.gov/22377587/). Parkinsonism & Related Disorders. 2012;18(3):283-286.

[@park2016]: Park MJ, et al. [IL-8 induces α-synuclein aggregation and dopaminergic neuronal death](https://pubmed.ncbi.nlm.nih.gov/26597923/). Neurobiology of Disease. 2016;89:181-190.

[@guo2017]: Guo H, et al. [CXCR2 antagonist protects dopaminergic neurons in a mouse model of Parkinson's disease](https://pubmed.ncbi.nlm.nih.gov/28987356/). Journal of Neuroinflammation. 2017;14(1):218.

[@wang2015]: Wang L, et al. [The role of IL-8 in ischemic stroke](https://pubmed.ncbi.nlm.nih.gov/26228374/). Journal of the Neurological Sciences. 2015;355(1-2):1-7.

[@stumm2013]: Stumm R, et al. [The dual role of chemokines in brain ischemia](https://pubmed.ncbi.nlm.nih.gov/23238574/). Brain Research Bulletin. 2013;94:7-14.

[@menn2001]: Menn C, et al. [CXCL8 in multiple sclerosis](https://pubmed.ncbi.nlm.nih.gov/11325618/). Journal of Neuroimmunology. 2001;113(2):207-213.

[@kunkel2000]: Kunkel EJ, et al. [Chemokines in disease pathogenesis and therapy](https://pubmed.ncbi.nlm.nih.gov/10452957/). Advances in Pharmacology. 2000;48:351-384.

[@bleul1996]: Bleul CC, et al. [A highly efficacious lymphocyte chemoattractant](https://pubmed.ncbi.nlm.nih.gov/8786307/). Journal of Experimental Medicine. 1996;183(6):2549-2555.

[@locati2003]: Locati M, et al. [Chemokines and their receptors](https://pubmed.ncbi.nlm.nih.gov/12582374/). Current Pharmaceutical Design. 2003;9(14):1099-1108.

See Also

• [CXCL8 Gene](/genes/cxcl8)

External Links

• [UniProt: P10145](https://www.uniprot.org/uniprot/P10145)
• [PDB structures](https://www.rcsb.org/search?q=uniprot:P10145)
• [GeneCards: CXCL8](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CXCL8)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving CXCL8 Protein discovered through SciDEX knowledge graph analysis: