Cxcl1

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.

In the CC chemokines, the cysteines follow each other directly, in the CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, in the CXXXC chemokines by 3 other amino acids. We show that CCL15 is processed in human synovial fluid by matrix metalloproteinases (MMPs) and serine proteases. They transmit their signals by binding to chemokine receptors via G-proteins. Some chemokines have a pro-inflammatory effect, others have a regulatory effect on the formation, homeostasis and proliferation of tissues.

CXCL1, also known as C-X-C Motif Chemokine Ligand 1, is expressed by macrophages, neutrophil granulocytes, mast cells and various other chemokines. It is produced and secreted by macrophages, neutrophil granulocytes, mast cells and various tumor cell lines. The CXCL1 gene is located on chromosome 4 in a gene cluster, in the vicinity of genes of other CXC chemokines. CXCL1 binds to the chemokine receptor CXCR2. CXCL1 is a potent chemoattractant for neutrophil granulocytes. Furthermore CXCL1 is a mitogenically active chemokine. It is involved in angiogenesis, embryonic development of the spinal cord, inflammatory processes, wound healing and tumorigenesis.

Inflammatory processes: The chemokine is active in the early phase of an ischemic stroke.

The CXCL1- CXCR2 axis appears to play a pathogenetic role in multiple sclerosis as well as in the inflammatory response in rheumatoid arthritis. CXCL1, together with other CXC chemokines(CXCL 2,6,8), is overexpressed in rosacea papulopustulosa

In the intestinal epithelium, the expression of the CXCL1 and CXCL2 genes can be upregulated by 5-fluorouracil (5-FU). Clinically induced 5-FU as a chemotherapeutic agent diarrhoea. Curcumin , an orange-yellow natural dye derived from curcuma longa of turmeric, can inhibit the expression of both genes by inhibiting NF-kappB. Progesterone and Calcitriol reduce the overexpression of CXCL1 and CXCL2 in ovarian and endometrial cancer.

CXCL1 and tumor growth: CXCL1 is increasingly expressed in gastric cancer and promotes tumor growth by activating the growth factor VEGF. It is involved in the pathogenesis of melanoma, bladder cancer and ovarian cancer.

1. Burnier A et al (2015) CXCL1 is elevated in the urine of bladder cancer patients. Knight plus 4:610.

2. Chintakuntlawar AV et al (2009) Chemokines CXCL1/KC and its receptor CXCR2 are responsible for neutrophil chemotaxis in adenoviral keratitis. J Interferon Cytokines Res 29:657-666.

3. De Filippo K et al (2013) Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation. Blood 121:4930-4937.

4. Imaizumi T et al (2015) Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells. Clin Exp Nephrol.19:761-770.

5. Kavandi L et al (2012) Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and CXCL2 in ovarian and endometrial cancer cells. J Cell Biochem113:3143-3152.

6. Mangahas CR et al (205) Endothelin-1 induces CXCL1 and CXCL8 secretion in human melanoma cells. J Invest Dermatol. 2005 Aug;125(2):307-11.

7. Losy J et al (2005) CXCL1 (GRO-alpha) chemokines in acute ischaemic stroke patients. Folia Neuropath 43:97102. https://www.ncbi.nlm.nih.gov/pubmed/16012911

8. Sakai H et al (2016) Curcumin Inhibits 5-fluorouracil-induced Up-regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development. Basic Clin Pharmacol Toxicol 119:540-547.

9. Wei ZW et al,(2015) CXCL1 promotes tumor growth through VEGF pathway activation and is associated with inferior survival in gastric cancer. Cancer Lett 359:335-343.