CXCL17 Human

VEGF Co-regulated Chemokine 1 Human Recombinant
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Description

Molecular Structure and Tissue Expression

CXCL17 is encoded by the CXCL17 gene located on human chromosome 19q13.2 . The protein contains six cysteine residues, forming a structure distinct from canonical CXC chemokines like CXCL8 . Mature CXCL17 is a 97-amino-acid peptide (~11 kDa) after cleavage of a 22-residue signal peptide .

Tissue Distribution

CXCL17 is constitutively expressed in mucosal tissues, including:

TissueExpression LevelFunction/PathologySource
LungHighHomeostatic macrophage recruitment; implicated in pulmonary fibrosis and asthma
Stomach (glandular)HighestAnti-inflammatory effects; alcohol-induced upregulation
IntestineModerateMucosal barrier maintenance; antimicrobial activity against pathogens
TumorsVariableAngiogenesis promotion in cancers (e.g., lung, liver); tumor progression

Biological Functions and Mechanisms

CXCL17 exhibits dual roles in homeostasis and inflammation, with unique anti-inflammatory properties.

Immune Cell Recruitment

  • Macrophages: Critical chemoattractant for lung macrophages; CXCL17 deficiency reduces alveolar macrophage populations by ~50% .

  • Monocytes/Dendritic Cells: Attracts quiescent monocytes and dendritic cells in vitro and in vivo .

  • Neutrophils: Modest chemotactic activity at high concentrations (5 μM) .

Anti-Inflammatory and Protective Effects

MechanismOutcomeSource
LPS-induced cytokine suppressionReduces IL-6, TNFα, and nitric oxide production in macrophages
Angiogenesis promotionInduces VEGF-A and COX-2 expression, supporting tissue repair
Antimicrobial activityDisrupts bacterial membranes (e.g., Staphylococcus aureus, E. coli)

Receptor Identification and Signaling

Despite initial attribution to GPR35 (dubbed CXCR8 in some studies), subsequent research disproved this . Current evidence suggests a distinct, unidentified GPCR mediates CXCL17’s effects:

Receptor CandidateEvidenceSource
GPR35Rejected; CXCL17 fails to activate GPR35 in functional assays
Unknown GPCRInduces ERK1/2 and P38 MAPK phosphorylation in macrophages; cAMP signaling in gastric cells

Clinical Implications and Disease Association

CXCL17’s dual roles in health and disease are context-dependent:

Pathogenic Roles

DiseaseRole of CXCL17Source
Pulmonary FibrosisElevated in bronchoalveolar lavage; linked to macrophage-driven fibrosis
AsthmaPromotes airway inflammation and macrophage infiltration
CancersAngiogenic factor in lung/hepatic tumors; tumor progression

Protective Roles

DiseaseRole of CXCL17Source
Pancreatic CancerSuppresses tumor growth; anti-angiogenic effects
Autoimmune DiseasesLimits pro-inflammatory cytokine production; hyporesponse in encephalomyelitis
Influenza A(H1N1)Diagnostic biomarker for severe disease; predicts mortality and renal failure

Diagnostic and Therapeutic Potential

ApplicationEvidenceSource
Diagnostic BiomarkerElevated serum CXCL17 differentiates pandemic influenza A(H1N1) from COVID-19 and tuberculosis
Therapeutic TargetInhibiting CXCL17 in pulmonary fibrosis/asthma; enhancing anti-inflammatory effects in autoimmune diseases

Product Specs

Introduction
Dendritic cell and monocyte chemokine-like protein (DMC/CXCL17/VEGF-correlated chemokine 1/VCC1) is a secreted molecule structurally similar to chemokines CXCL8/IL8 and CXCL14/BRAK. Primarily produced by airway and intestinal epithelium, CXCL17 selectively attracts inactive peripheral blood monocytes and dendritic cells. This chemokine also demonstrates increased expression in endothelial cells during tube formation. Notably, CXCL17, alongside angiogenesis-related chemokines CXCL1/GRO and CXCL8/IL8, exhibits correlated expression with VEGF in lung, breast, and esophageal tumors, suggesting a potential role in tumor angiogenesis. Sequence analysis reveals a high degree of conservation across species, with the mature Rat CXCL17 sharing 82% and 71% amino acid similarity with mouse and human CXCL17, respectively.
Description
Recombinant human CXCL17, expressed in E. coli, is a non-glycosylated polypeptide chain comprising 98 amino acids. This protein, with a molecular weight of 11.5 kDa, is purified using advanced chromatographic techniques.
Physical Appearance
White, lyophilized powder, sterile-filtered.
Formulation
The lyophilized CXCL17 protein was prepared in a 0.2µm filtered solution of phosphate-buffered saline (PBS) at pH 7.4, supplemented with 3% trehalose.
Solubility
To reconstitute, dissolve the lyophilized CXCL17 in sterile 18 MΩ·cm water to a concentration of at least 100 µg/ml. Further dilutions can be prepared in other aqueous solutions.
Stability
While the lyophilized CXCL17 remains stable at room temperature for up to 3 weeks, storage in desiccated conditions below -18°C is recommended. After reconstitution, the protein is stable at 4°C for 2-7 days. For prolonged storage, freeze at -18°C, ideally with a carrier protein like 0.1% HSA or BSA. Avoid repeated freeze-thaw cycles.
Purity
Purity exceeds 97.0% as determined by: (a) Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis. (b) Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis.
Biological Activity
The half-maximal effective concentration (ED₅₀), determined by the chemokine's ability to induce VEGF expression in murine endothelial cells, is less than 5.0 µg/ml. This corresponds to a specific activity greater than 200 IU/mg.
Synonyms
VEGF coregulated chemokine 1, C-X-C motif chemokine 17, Dendritic cell and monocyte chemokine-like protein, DMC, CXCL17, VCC1, Dcip1, VCC-1, UNQ473.
Source
Escherichia Coli.
Amino Acid Sequence
SSLNPGVARG HRDRGQASRR WLQEGGQECE CKDWFLRAPR RKFMTVSGLP KKQCPCDHFK GNVKKTRHQR HHRKPNKHSR ACQQFLKQCQ LRSFALPL.

Product Science Overview

Introduction

CXCL17 is strategically expressed in mucosal tissues and plays a significant role in the immune response. It is involved in the recruitment of immune cells, such as monocytes and dendritic cells, to sites of inflammation . This chemokine is also known for its broad antimicrobial activity, which includes disrupting bacterial membranes .

Preparation Methods

Recombinant human CXCL17 is typically produced using Escherichia coli (E. coli) expression systems . The protein is expressed as a fusion protein and then purified through various chromatographic techniques to achieve high purity levels. The recombinant protein is often lyophilized and can be reconstituted in sterile phosphate-buffered saline (PBS) for use in various applications .

Chemical Reactions Analysis

CXCL17 has been shown to induce the expression of vascular endothelial growth factor (VEGF) in endothelial cells, which is crucial for angiogenesis . This chemokine also upregulates the RNA levels of genes involved in angiogenesis, including VEGF-A and basic fibroblast growth factor (FGF) . Additionally, CXCL17 can induce the migration of CD14+ monocytes and CD11c+ immature dendritic cells from human peripheral blood .

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