CCL3 is a cytokine belonging to the CC chemokine family. Chemokines are a family of structurally related leukocyte chemoattractant cytokines that play a central role during immunoregulatory and inflammation processes. All chemokines contain four conserved cysteines linked by disulfide bonds, and two major subfamilies, namely CXC and CC, are defined on the basis of the first two cysteines which are separated by one amino acid or are adjacent. CCL3 is involved in the acute inflammatory state in the recruitment and activation of polymorphonuclear leukocytes.
C-C Motif Chemokine 3 (MIP-1 alpha,CCL3 ) is a member of the beta or CC subfamily of chemokines and is closely related to CCL4/MIP-1 beta. CCL3 expression can be induced in a variety of hematopoietic cells, fibroblasts, smooth muscle cells, and epithelial cells. Mature mouse CCL3 shares 73%, 91%, and 82% amino acid sequence identity with human, rat, and cotton rat CCL3, respectively. CCL3 exerts its biological functions through interactions with CCR1, CCR3, and CCR5. It is cleared from the extracellular space by internalization via the decoy chemokine receptor D6. CCL3 promotes the chemoattraction, adhesion to activated vascular endothelium, and cellular activation of many hematopoietic cell types including activated T cells, NK cells, neutrophils, monocytes, immature dendritic cells, and eosinophils. CCL3 is also known as stem cell inhibitor (SCI) and can inhibit the proliferation of hematopoietic progenitor cells. CCL3 bioactivity contributes to tumor metastasis and the inflammatory components of viral infection, rheumatoid arthritis, and hepatitis, although it also can suppress the replication of HIV.
CCL4 (C-C chemokine ligand 4), is a macrophage inflammatory protein with a chief effect in inflammation and immune-regulation, and was documented in cancer progression by promoting instability in the tumor environment. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) plays an important role in the pathogenesis and progression of cancer. In particular, higher serum CCL4 levels in patients with oral squamous cell carcinoma (OSCC) are associated with a more advanced stage of disease. CCL4 may be a new molecular therapeutic target for inhibition of lymphangiogenesis and metastasis in OSCC. CCL3 and CCL4 loci may be marker SNPs for risk of HCV treatment outcome. CCL4 can enhance the recruitment of preosteoclasts to bone in the early stage, and the reduction of CCR5 promotes osteoclastogenesis when RANKL is prevalent.
In mice , CCL6/C10 is expressed in cells from neutrophil and macrophage lineages , and can be greatly induced under conditions suitable for myeloid cell differentiation. It is highly expressed in bone marrow cultures that have been stimulated with the cytokine GM-CSF. Some low levels of gene expression also occur in certain cell lines of myeloid origin (e.g. the immature myeloid cell lines DA3 and 32D cl3 , and the macrophage cell line P388D) that can also be greatly induced in culture with GM-CSF. However , in activated T cell lines , expression of CCL6/C10 is greatly reduced.CCL6/C10 can also be induced in the Mouse lung by the cytokine interleukin 13
Chemokines are a family of small chemotactic cytokines, or proteins secreted by cells. Chemokines share the same structure similarities such as small size, and the presence of four cysteine residues in conserved locations in order to form their 3-dimensional shape. Some of the chemokines are considered pro-inflammatory which can be induced to recruit cells of the immune system to a site of infection during an immune response, while others are considered homeostatic and are implied in controlling the migration of cells during normal processes of tissue maintenance and development. There are four members of the chemokine family: C-C kemokines, C kemokines, CXC kemokines and CX3C kemokines. The C-C kemokines have two cysteines nearby the amino terminus. There have been at least 27 distinct members of this subgroup reported for mammals, called C-C chemokine ligands-1 to 28. Chemokine ligand 7(CCL7), also known as MCP-3, is a isform of the C-C chemokine subfamily of the chemokine family which is produced by certain tumor cells and by macrophages. It also own two adjacent N-terminal cysteine residues. Chemokine ligand 7(CCL7) spacifically attracts monocytes, and regulates macrophage function.
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