Ccl16

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.

CCL16, also known as chemokines (C-C motif) ligand 16 or "liver-expressed chemokine" (LEC), is a small, human cytokine that belongs to the CC chemokine family. The coding human CCL16 gene is located on chromosome Chr. 17 q11.2, together with other chemokine genes that belong to the CC gene family.

CCL16 is produced by numerous immune cells, such as dendritic cells, monocytes, macrophages (also alveolar macrophages), etc. Originally, CCL16 was discovered in activated monocytes after their stimulation by interleukin-10.

CCL16 is expressed in liver, thymus and spleen. CCL16 is a ligand for the chemokine receptors CCR1, CCR2, CCR5 and CCR8.

CCL16 has a chemoattractive and activating effect on monocytes (monocytes increasingly express CD80, CD86, CD40) and lymphocytes. Interleukin-10 and interferon gamma as well as microbial lipopolysaccharides can significantly increase the expression of this chemokine on monocytes.

In human synovial fluid, CCL16, like CCL15, is processed and activated by matrix metalloproteinases (MMPs) and serine proteases.

Chemokines play an essential role in the pathogenesis of sarcoidosis. In studies on larger patient groups with advanced type III sarcoidosis (D86.9) in bronchoalveolar lavage (BAL), the concentrations of the chemokines CCL16, CCL15, CCL24, CXCL8, CXCL9, CXCL10 and interleukin-16 were significantly increased. CCL16 expressions were also significantly overexpressed in eosinophilic pneumonia.

Furthermore, CCL16 together with interleukin-10 is increasingly expressed in ulcerative colitis.

1. Arakelyan A et al (2009) Protein levels of CC chemokine ligand (CCL)15, CCL16 and macrophage stimulating protein in patients with sarcoidosis. Clin Exp Immunol 155:457-465.
2. Cappello P et al (2004) CCL16/LEC powerfully triggers effector and antigen-presenting functions of macrophages and enhances T cell cytotoxicity. J Leukoc Biol 75:135-142 Caorsi C et al. (2008) CCL16 enhances the CD8+ and CD4+ T cell reactivity to human HER-2 elicited by dendritic cells loaded with rat ortholog HER-2 Int J Immunopathol Pharmacol 21:867 877
3. Musso T et al (2005) IL-10 enhances CCL2 release and chemotaxis induced by CCL16 in human monocytes. Int J Immunopathol Pharmacol 18: 39-349.
4. Nureki S et al (2009) Elevated concentrations of liver-expressed chemokine/CC chemokine ligand 16 in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia. Int Arch Allergy Immunol 150:282-290.
5. Pannellini T et al (2004) The expression of LEC/CCL16, a powerful inflammatory chemokine, is upregulated in ulcerative colitis. Int J Immunopathol Pharmacol 17:171-180.
6. Starr AE et al (2012) Biochemical analysis of matrix metalloproteinase activation of chemokines CCL15 and CCL23 and increased glycosaminoglycan binding of CCL16. J Biol Chem 287:5848-5860.