Ccl4

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. 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 and homeostasis of tissues.

CCL4, also known as "Macrophage inflammatory protein-1beta" or "MIP-1beta" is a CC chemokine that binds as a ligand for the CCR5 receptor. The coding CCL4 gene is located in the vicinity of the CCL3 gene on chromosome 17: 36.1 - 36.11.

Originally, the chemokine was named MIP-1. For about 3 decades now, 2 variants of MIP-1 have been identified under the names MIP-1-alpha and MIP-1-beta. They are classified as CCL3 and CCL4. Both chemokines overlap in their effect.

CCL4, like CCL3, is secreted by activated macrophages (e.g. after stimulation with bacterial endotoxins). Interferon gamma is able to suppress the expression of CCL4 and CCL3.

CCL4 is an attractor for NK cells, monocytes and other immune cells. CCL4 and CCL3 induce proinflammatory cytokines such as interleukin-1, interleukin-6 and TNF-alpha in fibroblasts and macrophages.

The chemokine receptor 4 (CCR4) is expressed by type 2 T-helper cells and is involved in the regulation of allergic tissue reactions.

In patients with hepatocellular carcinoma (C22.0) higher serum levels of thrombopoietin (TPO) and the chemokines CCL4. CCL5 and CXCL5 could be detected. High serum levels of CCL4 and CCL5 proved to be reliable diagnostic markers for hepatocellular carcinoma.

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