Ccl14

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 (see figure), in the CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, 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 formation, homeostasis and proliferation of tissues.

CCL14, also called chemokines (C-C motif) ligand 14 is a small human cytokine belonging to the CC chemokine family. The coding human CCL14 gene is located on chromosome 17q11.2, together with other chemokine genes belonging to the CC gene family. The chemokine has a 46% match of its amino acid composition with the chemokines CCL3 and CCL4.

CCL14 is expressed in various tissues such as spleen, bone marrow, liver, muscle and intestinal epithelia.

CCL14 binds to the chemokine receptors CCR1, CCR2 and CCR5 and to the HIV-1 co-receptor.

CCL14 is expressed together with CCL15 and CCL6 in intestinal epithelia. These chemokines are significantly upregulated in inflammatory (also microbially induced) intestinal diseases.

CCL14 is produced and secreted to a large extent together with the chemokines CCL3 and CCL2 by multiple myeloma cells.

CCL14 activates and attracts monocytes, T-lymphocytes, neutrophils and eosinophils. CCL14 increases the proliferation of CD34+ "myeloid progenitor" cells.

CCL14, together with other chemokines (e.g. CX3CL1), plays an activating and controlling role in the invasion of the human trophoblast.

In a special group of HIV-infected, non antivirally treated persons (so-called "elite controllers"), a special immunological constellation leads to a cessation of HIV infection. Of 87 cytokines measured, the chemokines CCL14, CCL21, CCL27 and XCL1 were significantly elevated in the elite controllers but not in the non-controllers. They are therefore likely to play a pathogenetic role in HIV infection.

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7. Li Y et al (2015) Chemokines CCL2, 3, 14 stimulate macrophage bone marrow homing, proliferation, and polarization in multiple myeloma. Oncotarget 6:24218-2429.