Cytokines & Chemokines

CCL18, is a novel CC chemokine that is highly homologous to MIP-1α (61% amino acid sequence identity). CCL18 cDNA encodes an 89 aa residue precursor protein with a 20 aa putative signal peptide that is cleaved to generate a 69 aa residue mature protein which lacks potential glycosylation sites. In vitro, CCL18 mRNA expression is induced in alternatively activated macrophages by Th2 cytokines such as IL-4, IL-10 and IL-13, and inhibited by IFN-γ. CCL18 mRNA is also expressed by GM-CSF/IL-4-induced monocyte-derived dendritic cells. In vivo, CCL18 is highly expressed in lung and placenta but is not expressed in epidermal Langerhans cells. Recombinant CCL18 has been shown to chemoattract naive T cells, but not monocytes or neutrophils.

Exodus-2/CCL21 is a novel CC chemokine discovered independently by three groups from the EST database, and shows 21-33% identity to other CC chemokines. Exodus-2 contains the four conserved cysteines characteristic of β chemokines plus two additional cysteines in its unusually long carboxyl terminal domain. It is expressed in lymph nodes of certain endothelial cells, and in the spleen and appendix. Exodus-2 chemoattracts T and B lymphocytes and inhibits hematopoiesis.

Exodus-2/CCL21 is a novel CC chemokine discovered independently by three groups from the EST database, and shows 21-33% identity to other CC chemokines. Exodus-2 contains the four conserved cysteines characteristic of β chemokines plus two additional cysteines in its unusually long carboxyl terminal domain. It is expressed in lymph nodes of certain endothelial cells, and in the spleen and appendix. Exodus-2 chemoattracts T and B lymphocytes and inhibits hematopoiesis.

CCL25 (thymus expressed chemokine) is a novel CC chemokine that is distantly related (approximately 20% amino acid sequence identity) to other CC chemokines. Mouse CCL25 cDNA has also been cloned and shown to encode a 144 aa protein that exhibits 49% aa sequence identity to human CCL25. The expresssion of human and mouse CCL25 was shown to be highly restricted to the thymus and small intestine. Although dendritic cells have been demonstrated to be the source of CCL25 production in the thymus, dendritic cells derived from bone marrow do not express CCL25.

CCL25 (thymus expressed chemokine) is a novel CC chemokine that is distantly related (approximately 20% amino acid sequence identity) to other CC chemokines. Mouse CCL25 cDNA has also been cloned and shown to encode a 144 aa protein that exhibits 49% aa sequence identity to human CCL25. The expresssion of human and mouse CCL25 was shown to be highly restricted to the thymus and small intestine. Although dendritic cells have been demonstrated to be the source of CCL25 production in the thymus, dendritic cells derived from bone marrow do not express CCL25.

The mouse homolog of ENA-78 is called LIX. ENA-78/LIX is a CXC chemokine that signals through the CXCR2 receptor. It is expressed in monocytes, platelets, endothelial cells, and mast cells. ENA-78/LIX is a chemoattractant for neutrophils. The three naturally occurring variants of human ENA-78; ENA 5-78, ENA 9-78 and ENA 10-78, contain 74, 70, and 69 amino acid residues, respectively, and possess the same biological activity. ENA-78/LIX contains the four conserved cysteine residues present in CXC chemokines, and also contains the 'ELR' motif common to CXC chemokine that bind to the CXCR1 and CXCR2 receptors.

The mouse homolog of ENA-78 is called LIX. ENA-78/LIX is a CXC chemokine that signals through the CXCR2 receptor. It is expressed in monocytes, platelets, endothelial cells, and mast cells. ENA-78/LIX is a chemoattractant for neutrophils. The three naturally occurring variants of human ENA-78; ENA 5-78, ENA 9-78 and ENA 10-78, contain 74, 70, and 69 amino acid residues, respectively, and possess the same biological activity. ENA-78/LIX contains the four conserved cysteine residues present in CXC chemokines, and also contains the 'ELR' motif common to CXC chemokine that bind to the CXCR1 and CXCR2 receptors.

IGF-BP3 is a 30 kDa cysteine-rich secreted protein. It is the major IGF binding protein present in the plasma of human and animals and it is also found in α-granules of platelets. In addition to its ability to modulate the activity of IGF-I and IGF-II, IGF-BP3 exerts inhibitory effects on follicle stimulating hormone (FSH) activity. Decreased plasma levels of IGF-BP3 often results in dwarfism, whereas elevated levels of IGF-BP3 may lead to acromegaly. The expression of IGF-BP3 in fibroblasts is stimulated by mitogenic growth factors such as Bombesin, Vasopressin, PDGF, and EGF.

IGF-BP3 is a 30 kDa cysteine-rich secreted protein. It is the major IGF binding protein present in the plasma of human and animals and it is also found in α-granules of platelets. In addition to its ability to modulate the activity of IGF-I and IGF-II, IGF-BP3 exerts inhibitory effects on follicle stimulating hormone (FSH) activity. Decreased plasma levels of IGF-BP3 often results in dwarfism, whereas elevated levels of IGF-BP3 may lead to acromegaly. The expression of IGF-BP3 in fibroblasts is stimulated by mitogenic growth factors such as Bombesin, Vasopressin, PDGF, and EGF.