CXCR1 Gene

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gene1211 wordssynced 2026-04-02

CXCR1 (C-X-C Motif Chemokine Receptor 1)

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CXCR1 (C-X-C Motif Chemokine Receptor 1)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CXCR1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CXCR1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>C-X-C Motif Chemokine Receptor 1</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>IL8RA, IL-8R1, CD128, CD181</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2q35</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[2915](https://www.ncbi.nlm.nih.gov/gene/2915)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[146929](https://www.omim.org/entry/146929)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>[ENSG00000163464](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00163464)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P41597](https://www.uniprot.org/uniprot/P41597)</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>350 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~40 kDa</td>
</tr>
<tr>
<td class="label">Ligand</td>
<td>Chemokine Family</td>
</tr>
<tr>
<td class="label">CXCL8 (IL-8)</td>
<td>CXC family</td>
</tr>
<tr>
<td class="label">CXCL6 (GCP-2)</td>
<td>CXC family</td>
</tr>
<tr>
<td class="label">CXCL1 (GRO-alpha)</td>
<td>CXC family</td>
</tr>
<tr>
<td class="label">CXCL7 (NAP-2)</td>
<td>CXC family</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Neutrophils</td>
<td>Highest</td>
</tr>
<tr>
<td class="label">Monocytes/Macrophages</td>
<td>High</td>
</tr>
<tr>
<td class="label">Microglia</td>
<td>Moderate-high</td>
</tr>
<tr>
<td class="label">T Cells</td>
<td>Low-moderate</td>
</tr>
<tr>
<td class="label">NK Cells</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Disease State</td>
<td>CXCR1 Expression</td>
</tr>
<tr>
<td class="label">Alzheimer's Disease</td>
<td>Increased</td>
</tr>
<tr>
<td class="label">Parkinson's Disease</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">Multiple Sclerosis</td>
<td>Upregulated</td>
</tr>
<tr>
<td class="label">Stroke/Ischemia</td>
<td>Rapidly increased</td>
</tr>
<tr>
<td class="label">ALS</td>
<td>Elevated</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Target</td>
</tr>
<tr>
<td class="label">Reparixin</td>
<td>CXCR1/2</td>
</tr>
<tr>
<td class="label">Danirixin</td>
<td>CXCR2</td>
</tr>
<tr>
<td class="label">SX-517</td>
<td>CXCR1</td>
</tr>
<tr>
<td class="label">Lidocaine derivatives</td>
<td>CXCR1/2</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/epilepsy" style="color:#ef9a9a">Epilepsy</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">59 edges</a></td>
</tr>
</table>

Overview

CXCR1 (C-X-C Motif Chemokine Receptor 1), also known as IL-8RA (Interleukin-8 Receptor Alpha), is a G protein-coupled receptor (GPCR) that specifically binds interleukin-8 (IL-8/CXCL8) and granulocyte colony-stimulating factor (G-CSF)[@liu2019]. Originally characterized for its role in neutrophil recruitment and activation during acute inflammation, CXCR1 is now recognized as a significant contributor to chronic neuroinflammatory processes in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and multiple sclerosis[@bhatia2005].

In the central nervous system (CNS), CXCR1 is expressed on microglia, astrocytes, and neurons, where its activation by IL-8 (produced in response to pathological stimuli) triggers pro-inflammatory signaling cascades that contribute to neuronal dysfunction and death[@rivest2009].

Gene Information

Molecular Function

Ligand Binding

CXCR1 is a high-affinity receptor for:

Signal Transduction Pathways

Upon IL-8 binding, CXCR1 activates multiple intracellular signaling cascades:

Mermaid diagram (expand to render)

Key Signaling Pathways

PI3K/Akt: Cell survival, migration, metabolic regulation

MAPK/ERK: Proliferation, cytokine production, cell differentiation

PLC/IP3: Calcium mobilization, granule release

JAK/STAT: Gene transcription, inflammatory response

Receptor Regulation

Desensitization: GRK-mediated phosphorylation leads to β-arrestin recruitment
Internalization: Receptor internalization via clathrin-coated pits
Recycling: Receptor returns to cell surface or is degraded

Expression Pattern

Immune Cell Expression

CNS Expression

Microglia:

Resting microglia: Low CXCR1 expression
Activated microglia: Upregulated CXCR1
Proximity to amyloid plaques: Elevated expression

Astrocytes:

Reactive astrocytes: Increased CXCR1
Inflammatory conditions: Enhanced signaling

Neurons:

Low baseline expression
Upregulation in pathological states
May contribute to excitotoxicity

Expression in Disease

Role in Neurodegeneration

Alzheimer's Disease

CXCR1 plays a significant role in AD pathogenesis:

Microglial Activation[@swardfager2010]:

IL-8 levels are elevated in AD brains and cerebrospinal fluid
CXCR1+ microglia surround amyloid plaques
Activation leads to pro-inflammatory cytokine release
Sustained inflammation contributes to neuronal dysfunction

Neuroinflammation Cascade:

Amyloid-beta accumulation → IL-8 production by astrocytes/microglia

IL-8 binding to CXCR1 on microglia → activation

Pro-inflammatory cytokine release (TNF-α, IL-1β, IL-6)

Chronic neuroinflammation → synaptic loss, neuronal death

Research Findings[@bhatia2005]:

CXCR1 expression colocalizes with amyloid plaques
IL-8/CXCR1 axis amplifies neuroinflammation
Correlation between CXCR1 and disease severity

Parkinson's Disease

In PD, CXCR1 contributes to:

Substantia Nigra Inflammation[@zhao2018]:

Elevated IL-8 in PD substantia nigra
CXCR1 activation on microglia promotes M1 phenotype
Inflammatory mediators contribute to dopaminergic neuron death
Neuroinflammation exacerbates alpha-synuclein pathology

Mechanistic Pathways:

CXCR1 signaling → oxidative stress
Cytokine release → mitochondrial dysfunction
Chronic activation → progressive neurodegeneration

Multiple Sclerosis

Demyelination: CXCR1+ immune cells contribute to myelin damage
Lesion Formation: Active MS lesions show elevated CXCR1
Blood-Brain Barrier Disruption: CXCR1 mediates immune cell trafficking

Amyotrophic Lateral Sclerosis

Motor Neuron Inflammation: CXCR1 on activated microglia
Disease Progression: Inflammatory signaling contributes to motor neuron loss
Therapeutic Target: CXCR1 antagonists under investigation

Stroke and Ischemia

Post-Ischemic Inflammation: Rapid IL-8 elevation
Neutrophil Recruitment: CXCR1 mediates post-injury inflammation
Secondary Damage: Inflammatory cascade exacerbates injury

Therapeutic Implications

CXCR1/2 Antagonists

Several small molecule antagonists have been developed:

Clinical Applications

Neuroinflammation Modulation: Reduce chronic inflammation
Microglial Activation: Shift from M1 to M2 phenotype
Neuroprotection: Prevent inflammatory neuron loss

Challenges

Receptor Redundancy: Multiple chemokines can signal through CXCR1/2
Acute vs Chronic: Different effects in acute vs chronic inflammation
BBB Penetration: Drug delivery to CNS is challenging

Therapeutic Strategies

Small Molecule Inhibitors: Systemic administration

Monoclonal Antibodies: Target circulating IL-8 or CXCR1

ASO Therapy: Reduce IL-8 expression

Gene Therapy: Modulate receptor expression

Signal Transduction in Neurodegeneration

Mermaid diagram (expand to render)

Clinical Significance

Biomarkers

Serum IL-8: Elevated in AD and PD
CSF IL-8: Correlates with disease progression
CXCR1 Expression: On circulating immune cells

Diagnostic Applications

Imaging: PET ligands for CXCR1 under development
Expression Analysis: CXCR1 on peripheral monocytes
Disease Monitoring: IL-8 levels as progression marker

Research Applications

In Vitro Models: Primary microglia culture
Animal Models: Transgenic mice, toxin models
Clinical Trials: CXCR1/2 antagonists in neurodegenerative disease

Key Publications

[Liu et al., CXCR1/2 in neuroinflammation and neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31127022/)

[Bhatia et al., IL-8 and CXCR1 in AD (2005)](https://pubmed.ncbi.nlm.nih.gov/15893604/)

[Glass et al., Inflammation in neurodegeneration (2006)](https://pubmed.ncbi.nlm.nih.gov/16439142/)

[Rivest et al., IL-8 signaling in neuroinflammation (2009)](https://pubmed.ncbi.nlm.nih.gov/19818653/)

[Horuk et al., IL-8 receptor molecular characterization (1994)](https://pubmed.ncbi.nlm.nih.gov/7964247/)

[Wood et al., Chemokine receptors on microglia (2006)](https://pubmed.ncbi.nlm.nih.gov/16574082/)

[Galimberti et al., IL-1beta and IL-1RA in AD (2005)](https://pubmed.ncbi.nlm.nih.gov/16006667/)

[Zhao et al., CXCR1/2 in PD and neuroinflammation (2018)](https://pubmed.ncbi.nlm.nih.gov/29753917/)

[Reaux-Le Goazigo et al., Chemokines in brain (2012)](https://pubmed.ncbi.nlm.nih.gov/23316146/)

[Swardfager et al., Meta-analysis of cytokines in AD (2010)](https://pubmed.ncbi.nlm.nih.gov/20692634/)

[Lucin & Wyss-Coray, CX3CL1-CX3CR1 in AD (2010)](https://pubmed.ncbi.nlm.nih.gov/20094918/)

[Cunningham et al., Systemic inflammation in AD progression (2013)](https://pubmed.ncbi.nlm.nih.gov/23831254/)

[White et al., Chemokine signaling in neuropathic pain (2011)](https://pubmed.ncbi.nlm.nih.gov/21306667/)

[Tripathy et al., CXCR1/2 antagonists in neuroinflammation (2018)](https://pubmed.ncbi.nlm.nih.gov/29653269/)

External Resources

[NCBI Gene - CXCR1](https://www.ncbi.nlm.nih.gov/gene/2915)
[UniProt - P41597](https://www.uniprot.org/uniprot/P41597)
[Ensembl - CXCR1](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00163464)
[OMIM - 146929](https://www.omim.org/entry/146929)

Pathway Diagram

The following diagram shows the key molecular relationships involving CXCR1 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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CXCR1 Gene

CXCR1 (C-X-C Motif Chemokine Receptor 1)

CXCR1 (C-X-C Motif Chemokine Receptor 1)

Overview

Gene Information

Molecular Function

Ligand Binding

Signal Transduction Pathways

Key Signaling Pathways

Receptor Regulation

Expression Pattern

Immune Cell Expression

CNS Expression

Expression in Disease

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Multiple Sclerosis

Amyotrophic Lateral Sclerosis

Stroke and Ischemia

Therapeutic Implications

CXCR1/2 Antagonists

Clinical Applications

Challenges

Therapeutic Strategies

Signal Transduction in Neurodegeneration

Clinical Significance

Biomarkers

Diagnostic Applications

Research Applications

Key Publications

External Resources

See Also

Pathway Diagram