Ccl19

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. 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.

CCL19, also known as C-C motif chemokine ligand 19, or "macrophage inflammatory protein-3-beta" or MIP-3-beta, is a small human cytokine belonging to the CC chemokine family. It is encoded by the CCL19 gene on chromosome 9. CCL9 (together with CCL22) is a ligand for the chemokine receptor CCR7.

CCL19 is a protein that is involved in numerous inflammatory processes. CCL19 is preferably expressed in the thymus and lymph nodes. But also to a lesser extent in trachea and colon, stomach, small intestine, kidney, and spleen.

CCL19 is chemotactic for various immune cells, including dendritic cells, antigen-activated B cells and CCR7-positive central T memory cells. CCL19 has no chemotactic effect on granulocytes and monocytes.

The CCL19 protein level was significantly upregulated in patients with chronic rhinosinusitis (with or without nasal polyps) and is further increased in patients with eosinophilic chronic rhinosinusitis compared to the non- eosinophilic forms. CCL19 was expressed by CD68+ macrophages.

In coronary artery disease (I25.9), increased expression of CCL19 and CCL21 was found in larger collectives in lesioned coronary arteries (as well as in the serum of these patients); analogous findings were found in plaques of carotid arteries in AVK (I63.0).

In prostate carcinoma cells, CCL19 and its receptor protein CCR7 were found to be significantly elevated, suggesting that the CCL19/CCR7 cytokine axis plays a role in the pathogenesis of this carcinoma. It remains to be seen to what extent therapeutic consequences can be drawn from this.

In systemic scleroderma (systemic sclerosis), the chemokines CCL19, CCL18 and CXCL13 are increasingly expressed in lesioned skin. The expression of CCL19 correlates with vascular inflammation in diffuse systemic scleroderma. CCL19 was mainly expressed in activated monocytes.

1. Akhavanpoor M det al (2014) CCL19 and CCL21 modulate the inflammatory milieu in atherosclerotic lesions. Drug of Devel Ther 8:2359 2371.
2. Marsland BJ et al (2005) CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells. Immunity 22:493-505.
3. Mathes AL et al (2014) Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin. Ann Rheum Dis 73:1864-1872.
4. Peng C et al (2015) The effect of CCL19/CCR7 on the proliferation and migration of cell in prostate cancer. Tumour Biol 36:329-335.
5. Zou Y et al (2016) Characteristic expression and significance of CCL19 in different tissue types in chronic rhinosinusitis. Exp Ther Med 11:140-146.
6. Zhang W et al (2014) Matrix metalloproteinase-9 is up-regulated by CCL19/CCR7 interaction via PI3K/Akt pathway and is involved in CCL19-driven BMSCs migration. Biochem Biophys Res Commun 451:222-228.