Cxcl5

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, some virus types and bacteria. In humans, about 50 chemokines are currently known. A strongly conserved structural feature of all chemokines is a fixed group of cysteine residues that is stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for its fixed 3-dimensional structure (see below chemokines).

In the CC-chemokines the cysteines follow each other directly, in the CXC-chemokines they are separated by 1 (see figure), in the CXXXC-chemokines by 3 other amino acids. Chemokines are produced and secreted by a large number of immune cells. They mediate their signals by means of specific chemokine receptors via G-proteins.

The fact that chemokines and their receptors are not only expressed on inflammatory cells, but also by epithelial cells, mesenchymal cells, neurogenic cells, endothelial cells, and various tumor cell lines, suggests that they participate in numerous regulatory cell functions.

CXCL5, also known as C-X-C motif chemokine 5 is a small surface protein from the group of CXC chemokines that is involved in the immune response and is further expressed in a number of malignant tumors. Together with other chemokines(CXCL1, CXCL2, CXCL3, CXCL7, CXCL8), CXCL5 is a ligand for the chemokine receptor CXCR2. CXCL5 is encoded by the CXCL5 gene located on chromosome 4 together with other CXC chemokines.

CXCL5 primarily has a chemotactic and activating effect on neutrophil granulocytes, especially during an acute inflammatory phase. The chemokine is also expressed by eosinophil granulocytes, among others. Its expression can be suppressed by interferon gamma.

CXCL5 is also significantly expressed in arteriosclerotic plaques (chronic inflammatory tissue reaction).

CXCL5 is overexpressed in numerous malignant tumors such as colorectal carcinomas, bladder carcinomas and non-small cell lung carcinomas (NSCLC). These overexpressions are associated with a poor prognosis of the tumors. Osteosarcomas also show a significant increase in CXCL5 expression.

Animal experiments have shown that CXCL5 and CXCR2 are upregulated in neuropathic pain after nerve injury and apparently play a role in pain perception.

CXCL5 is also a key mediator of pain induction in sunburn.

In human skin, a direct relationship between UVB dose and CXCL5 concentration could be established. Cell cultures have shown that fibroblasts, but not keratinocytes, are able to produce the chemokine CXCL5 in addition to immune cells.

1. Dang H et al (2017) CXCL5 Plays a Promoting Role in Osteosarcoma Cell Migration and Invasion in Autocrine- and Paracrine-Dependent Manners. Oncol Res 25:177-186.
2. Han N et al (2015) DACH1 inhibits lung adenocarcinoma invasion and tumor growth by repressing CXCL5 signaling.Oncotarget 6:5877-5888.
3. Enriches O et al (2015) UV radiation induces CXCL5 expression in human skin. Exp Dermatol 24:309-312.
4. Xu W et al (2016) Spinal CXCL5 contributes to nerve injury-induced neuropathic pain via modulating GSK-3β phosphorylation and activity in rats. Neurosci Lett 634:52-59.
5. Zhao J et al (2017) Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways. Mol Cancer 16:70.
6. Zhu X et al (2016) CXCL5 is a potential diagnostic and prognostic marker for bladder cancer patients. Tumour Biol 37:4569-4577.