Cytokines & Chemokines

CCL11 is a potent eosinophil chemoattractant that was originally purified from bronchoalveolar lavage fluid of guinea pigs sensitized by aerosol challenge with ovalbumin. Human CCL11 cDNA encodes a 97 amino acid residue precursor protein from which the aminoterminal 23 amino acid residues are cleaved to generate the 74 amino acid residue mature human CCL11. At the protein sequence level, mature human CCL11 is approximately 60% identical to mature mouse and guinea pig CCL11. Human CCL11 is chemotactic for eosinophils, but not mononuclear cells or neutrophils. The CC chemokine receptor 3 (CCR3) has now been identified to be a specific human CCL11 receptor. CCR3 has also been shown to serve as a cofactor for a restricted subset of primary HIV viruses and binding of CCL11 to CCR3 inhibited infection by the HIV isolates.

The Trefoil Factor peptides (TFF1, TFF2 and TFF3) are secreted in the gastrointestinal tract, and appear to play an important role in intestinal mucosal defense and repair. TFF-3 is expressed by goblet cells and in the uterus, and has also been shown to express in certain cancers, including colorectal, hepatocellular, and in biliary tumors. TFF3 may be useful as a molecular marker for certain types of cancer, but its role, if any, in tumorigenesis is unknown. TFF3 also promotes airway epithelial cell migration and differentiation.

The Trefoil Factor peptides (TFF1, TFF2 and TFF3) are secreted in the gastrointestinal tract, and appear to play an important role in intestinal mucosal defense and repair. TFF-3 is expressed by goblet cells and in the uterus, and has also been shown to express in certain cancers, including colorectal, hepatocellular, and in biliary tumors. TFF3 may be useful as a molecular marker for certain types of cancer, but its role, if any, in tumorigenesis is unknown. TFF3 also promotes airway epithelial cell migration and differentiation.

Interferon-Omega (IFN-ω) coded by IFNW1 gene in human, is a number of the type I interferon family, which includes IFN-a, IFN-β, and IFN-ω. The IFNAR-1/IFNAR-2 receptor complex can help with the signal transduction, followed the antiviral or the antiproliferative actions. IFN-ω is derived from IFN-a/β and share 75% sequence with IFN-a. It has two intramolecular disulfide bonds which are crucial for activities. Mire-Sluis et al have described bioassays for IFN-α, IFN-β, and IFN-ω that exploit the ability of these factors to inhibit proliferation of TF-1 cells induced by GM-CSF. The bioassays can be used also with Epo and TF-1 cells, or Epo and Epo-transfected UT-7 cells.

Members of the Hedgehog (Hh) family are highly conserved proteins which are widely represented throughout the animal kingdom. The three known mammalian Hh proteins, Sonic (Shh), Desert (Dhh) and Indian (Ihh) are structurally related and share a high degree of amino-acid sequence identity (e.g., Shh and Ihh are 93% identical). The biologically active form of Hh molecules is obtained by autocatalytic cleavage of their precursor proteins and corresponds to approximately the N-terminal one half of the precursor molecule. Although Hh proteins have unique expression patterns and distinct biological roles within their respective regions of secretion, they use the same signaling pathway and can substitute for each other in experimental systems.

Members of the Hedgehog (Hh) family are highly conserved proteins which are widely represented throughout the animal kingdom. The three known mammalian Hh proteins, Sonic (Shh), Desert (Dhh) and Indian (Ihh) are structurally related and share a high degree of amino-acid sequence identity (e.g., Shh and Ihh are 93% identical). The biologically active form of Hh molecules is obtained by autocatalytic cleavage of their precursor proteins and corresponds to approximately the N-terminal one half of the precursor molecule. Although Hh proteins have unique expression patterns and distinct biological roles within their respective regions of secretion, they use the same signaling pathway and can substitute for each other in experimental systems.

Interleukin-1 alpha (IL-1α) is a non-secreted proinflammatory cytokine produced in a variety of cells including monocytes, tissue macrophages, keratinocytes and other epithelial cells. Both IL-1αand IL-1β binds to the same receptor and has similar if not identical biological properties. These cytokines have a broad range of activities including, stimulation of thymocyte proliferation, by inducing IL-2 release, B-cell maturation and proliferation, mitogenic FGF-like activity and the ability to stimulate the release of prostaglandin and collagenase from synovial cells. However, whereas IL-1β is a secreted cytokine, IL-1α is predominantly a cell-associated cytokine.

Interleukin-1 alpha (IL-1α) is a non-secreted proinflammatory cytokine produced in a variety of cells including monocytes, tissue macrophages, keratinocytes and other epithelial cells. Both IL-1αand IL-1β binds to the same receptor and has similar if not identical biological properties. These cytokines have a broad range of activities including, stimulation of thymocyte proliferation, by inducing IL-2 release, B-cell maturation and proliferation, mitogenic FGF-like activity and the ability to stimulate the release of prostaglandin and collagenase from synovial cells. However, whereas IL-1β is a secreted cytokine, IL-1α is predominantly a cell-associated cytokine.

Human Bone Morphogenetic Protein-2 (BMP-2) is a bone-growth regulatory factor and belongs to the transforming growth factor-beta (TGF-beta) superfamily. Human Bone Morphogenetic Protein-2 (BMP-2) is synthesized as large precursor molecule (Met1-Arg396, with a signal peptide from Met1 to Gly23), propeptide (Leu24-Arg282) of which is cleaved by PCSK5 (Proprotein Convertase Subtilisin/Kexin type 5). The active form consists of a dimer of two identical proteins which are linked by a disulfide bond at Cys360. It plays an important role in the development of bone and cartilage, cardiac cell differentiation and epithelial to mesenchymal transition. It is also involved in the hedgehog pathway, TGF-beta signaling pathway, and in cytokine-cytokine receptor interaction.