Ccl13

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signaling proteins). They are found in all vertebrates, some virus species and bacteria. Around 50 chemokines are currently known in humans. 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 their fixed 3-dimensional structure.

In the CC chemokines, the cysteines follow each other directly, in the CXC chemokines they are separated by 1 amino acid (CC = acronym for cysteine-cysteine), in the CXXXC chemokines by 3 other amino acids. Chemokines are produced and secreted by a large number of immune cells. 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 development, homeostasis or proliferation of tissues.

CCL13 (CC-chemokine ligand 13) is a non-glycosylated, 8.6 kDa polypeptide, a cytokine from the CC chemokine family. The CCL13 gene (MCP-4 gene) is located on chromosome 17 in humans, together with a larger group of other C-C chemokines.

CCL13 is involved in numerous inflammatory processes. It is therefore the target of explorative and therapeutic approaches.

The chemokine has a chemotactic effect on monocytes, eosinophil and basophil granulocytes (but not on neutrophil granulocytes) as well as on T lymphocytes and immature dendritic cells (Mendez-Enriquez E et al. 2013). CCL13 binds to the G-protein-coupled chemokine receptors CCR2, CCR3 and CCR5. The chemokine is induced by the cytokines interleukin-1 and TNF-alpha.

In osteoarthritis of the knee, CCL13 is increasingly produced in both serum and synovial fluid and can serve as an activity marker. In rheumatoid arthritis, it has been shown that the "MCP-4/CCL13" gene coding for CCL13 is significantly elevated in chondrocytes.

Serum CCL13 is elevated in patients with systemic scleroderma, but not in patients with systemic lupus erythematosus, dermatomyositis or in patients with atopic eczema.

In allergic rhinitis , the chemokines CCL13 and eotaxin-3 in nasal secretion are several times higher. In contrast, the interleukin-4 and IL-10 were found to be significantly lower (also in comparison to healthy volunteers). Furthermore CCL13 is involved in the pathogenesis of bronchial asthma.

CCL13 seems to have a role in the invasion of monocytes into the vessel wall in arteriosclerosis.

1. Baumann R et al (2013) Comparison of the nasal release of IL-4, IL-10, IL-17, CCL13/MCP-4, and CCL26/eotaxin-3 in allergic rhinitis during season and after allergen challenge. At J Rhinol Allergy 27:266-272.
2. Gao F et al (2015) Association of CCL13 levels in serum and synovial fluid with the radiographic severity of knee osteoarthritis. J Investig Med 63:545-547.
3. Iwamoto T et al (2006) Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage from patients with rheumatoid arthritis. Rheumatology (Oxford) 45:421-424.
4. Mendez-Enriquez E et al (2013) The multiple faces of CCL13 in immunity and inflammation. Inflammopharmacology 21:397-406 Yanaba K et al. (2010) CCL13 is a promising diagnostic marker for systemic sclerosis. Br J Dermatol 162:332-336.