The chemokine (C-C motif) ligand 2 (CCL2), also known as monocyte chemoattractant protein (MCP)-1 and small inducible cytokine A2 (SCYA2)), is a small cytokine that belongs to the CC chemokine family responsible for monocyte attraction. Its cognate receptor, CCR2, play a critical role in regulating nociceptive processes during neuropathic pain. Both CCL2 and CCR2 are implicated in induction of autoimmunity. CCL2 recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection. Recently research also showed that CCL2 might be useful as a biomarker of fibrosis as well as a target for therapeutic intervention.
Human C-X-C Motif Chemokine Ligand 10 (CXCL10) is a non-ELR chemokine secreted by various cell types; such as monocytes; endothelial cells and fibroblasts; in response to IFN-γ. CXCL10 functions via chemokine receptor CXCR3. CXCL10 has been attributed to several roles; such as chemoattraction for activated T-lymphocytes; inhibition of angiogenesis; and antitumor activity.
CXCL11, also known as I-TAC, SCYB9B, H174 and beta -R1, is a non-ELR CXC chemokine. CXCL11 cDNA encodes a 94 amino acid (aa) residue precursor protein with a 21 aa residue putative signal sequence, which is cleaved to form the mature 73 aa residue protein. CXCL11 shares 36% and 37% amino acid sequence homology with IP-10 and MIG (two other known human non-ELR CXC chemokines), respectively. CXCL11 is expressed at low levels in normal tissues including thymus, spleen and pancreas. The expression of CXCL11 mRNA is radically up regulated in IFN-gamma and IL-1 stimulated astrocytes. Moderate increase in expression is also observed in stimulated monocytes. CXCL11 has potent chemoattractant activity for IL-2 activated T cells and transfected cell lines expressing CXCR3, but not freshly isolated T cells, neutrophils or monocytes. The gene encoding CXCL11 has been mapped to chromosome 4.
Chemotactic for B-lymphocytes but not for T-lymphocytes, monocytes and neutrophils. Does not induce calcium release in B-lymphocytes. Binds to BLR1/CXCR5.
Chemokine (C-X-C Motif) Ligand 9 (CXCL9) belongs to the intercrine alpha (chemokine CXC) family. It is secreted by interferon stimulated monocytes, macrophages and endothelial cells, which elicits chemotactic functions by interacting with the chemokine receptor CXCR3. CXCL9 acts as a Th1 (type 1 helper T) cell chemoattractant and plays a role in the growth, activation and movement of cells associated with immune and inflammatory responses, and in tumour growth inhibition. It is closely related to two other CXC chemokines called CXCL10 and CXCL11, whose genes are located near the gene for CXCL9 on human chromosome 4.
EGF is the founding member of the EGF-family of proteins. Members of this protein family have highly similar structural and functional characteristics. EGF contains 9 EGF-like domains and 9 LDL-receptor class B repeats. Human EGF is a 6045-Da protein with 53 amino acid residues and three intramolecular disulfide bonds. As a low-molecular-weight polypeptide, EGF was first purified from the mouse submandibular gland, but since then it was found in many human tissues including submandibular gland, parotid gland. It can also be found in human platelets, macrophages, urine, saliva, milk, and plasma. EGF is a growth factor that stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. It results in cellular proliferation, differentiation, and survival. Salivary EGF, which seems also regulated by dietary inorganic iodine, also plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. EGF acts by binding with high affinity to epidermal growth factor receptor on the cell surface and stimulating the intrinsic protein-tyrosine kinase activity of the receptor. The tyrosine kinase activity, in turn, initiates a signal transduction cascade that results in a variety of biochemical changes within the cell - a rise in intracellular calcium levels, increased glycolysis and protein synthesis, and increases in the expression of certain genes including the gene for EGFR - that ultimately lead to DNA synthesis and cell proliferation.
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