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Lymphotoxin-alpha (LT-alpha or LTA) belongs to the TNF ligand superfamily, which bind the same TNF receptor and mediate similar pleiotropic effect. LTA is a proinflammatory cytokine with important biological activity and immunomodulatory function and is known to influence a variety of cellular response. Furthermore, LTA mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and has a role in apoptosis. LTA is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchors lymphotoxin-alpha to the cell surface. LTA, which is located within the MHC III region of chromosome 6, shows close relation to the HLA class I (HLA-B) and class II (HLA-DR) genes. Polymorphism in the LTA gene appears to contribute to infectious disease susceptibility and infection. Genetic variations in the LTA gene are linked to susceptibility to leprosy type 4 and psoriatic arthritis.

PTX3 is part of the pentraxin family sharing the C-terminal domain with short pentraxins and containing a unique N-terminal domain. PTX3 is produced and released at inflammatory sites by various cell types including monocytes/macrophages, endothelial cells, vascular smooth muscle cells, fibroblasts, and adipocytes. PTX3 is involved in the regulation of innate resistance to pathogens, inflammatory reactions, possibly clearance of self-components and female fertility. PTX3 is used as a marker for disease activity of psoriasis. High serum PTX3 levels are associated with the disease severity of systemic sclerosis. Elevated serum PTX3 is associated with pulmonary fungal infections.

Ectodysplasin A Receptor, also known as EDAR belongs to the tumor necrosis factor receptor family. EDAR is a receptor for the soluble ligand ectodysplasin A, and is capable of activating the nuclear factor-kappaB, JNK, as well as caspase-independent cell death pathways. EDAR is necessary for the development of hair, teeth, and other ectodermal derivatives. Furthermore, mutations in EDAR resulted in autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia.

Tissue factor is well-known as the main cellular initiator of blood coagulation. The Tissue factor gene encodes coagulation factor III which is a cell surface glycoprotein that enables cells to initiate the blood coagulation cascades, and functions as the high-affinity receptor for the coagulation factor VII. Following vessel injury, the Tissue Factor and Factor VIIa complex activates the coagulation protease cascade, which leads to fibrin deposition and activation of platelets. The ensuing complex presents a catalytic event, which is responsible for initiation of the coagulation protease cascades by specific limited proteolysis. Therefore, Tissue factor has a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. Tissue Factor can also be stimulated by the inflammatory mediators interleukin 1 and TNF, as well as by endotoxin, to appear on monocytes and vascular endothelial cells as a component of cellular immune response.
Tissue factor is the only one in the coagulation pathway for which a congenital deficiency has not been described. Certain levels of Tissue Factor are essential for the maintained viability and growth of endothelium and Tissue Factor-expressing tumor cells. Additionally, abnormal Tissue Factor expression inside the vasculature initiates life threatening thrombosis in various diseases, for example sepsis, atherosclerosis, and cancer. Alternative spliced Tissue Factor expression advances tumor growth, and is linked to increased tumor cell proliferation and angiogenesis in pancreatic cancer.

CD27 belongs to the TNF-receptor superfamily. CD27 is necessary for initiation and long-term maintenance of T cell immunity. CD27 binds to ligand CD70, and has a crucial role in regulating B-cell activation and immunoglobulin synthesis. The CD27 receptor transduces signals which result in the activation of NF-kappaB and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 mediate the signaling process of CD27. CD27-binding protein (SIVA), which is a proapoptotic protein, can bind to the CD27 receptor and is believed to have a significant role in the apoptosis induced by CD27.

EDA2R (ectodysplasin A2 receptor) mediates the activation of the NF-kappa-B and JNK pathways. Activation seems to be mediated through binding to TRAF3 and TRAF6. In addition, Mutations in EDA give rise to a clinical syndrome characterized by loss of hair, sweat glands, and teeth. EDA2R specifically binds to EDA-A2 isoform. This protein is a type III transmembrane protein of the TNFR (tumor necrosis factor receptor) superfamily, and contains 3 cysteine-rich repeats and a single transmembrane domain however it lacks an N-terminal signal peptide. Alternatively spliced transcript variants have been found for this gene. Among the diseases associated with EDA2R are ectodermal dysplasia 1, hypohidrotic, x-linked, and hypohidrotic ectodermal dysplasia.

RANK, is part of the tumor necrosis factor receptor family. RANK is widely expressed with uppermost levels in the skeletal muscle, thymus, liver, colon, small intestine, adrenal gland as well as dendritic cells. Furthermore, in activated human peripheral blood T lymphocytes, RANK expression is induced by IL4 and TGF-b.

RANKL binds to tnfrsf11b/opg and to tnfrsf11a/rank. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive t-cell proliferation. May be an important regulator of interactions between t-cells and dendritic cells and may play a role in the regulation of the t-cell-dependent immune response. sRANKL may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

CD40L or CD154 is a membrane glycoprotein and differentiation antigen expressed on the surface of T-cells. The CD40 ligand stimulates B-cell proliferation and secretion of all immunoglobulin isotypes in the presence of cytokines. CD40 ligand has been shown to induce cytokine production and tumoricidal activity in peripheral blood monocytes. It also costimulates proliferation of activated T-cells and this is accompanied by the production of IFN-gamma , TNF-alpha , and IL2.

CD40L or CD154 is a membrane glycoprotein and differentiation antigen expressed on the surface of T-cells. The CD40 ligand stimulates B-cell proliferation and secretion of all immunoglobulin isotypes in the presence of cytokines . CD40 ligand has been shown to induce cytokine production and tumoricidal activity in peripheral blood monocytes. It also costimulates proliferation of activated T-cells and this is accompanied by the production of IFN-gamma , TNF-alpha , and IL2 .

The Trefoil Factor peptides (TFF1, TFF2 and TFF3) are stable secretory proteins expressed in the gastrointestinal tract (gastric mucosa), and are involved in intestinal mucosal defense and repair. TFF1 is an essential protein for normal differentiation of the antral and pyloric gastric mucosa and functions as a gastric-specific tumor suppressor gene. TFF1 is a stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. TFF1 protects the mucosa from isults, stabilizes the mucus layer, & affects healing of the epithelium. TFF1 is commonly expressed in tumors. TFF1 is related with the cell membrane of MCF-7 cells. High levels of TFF1 and TFF2 are found in serum from inflammatory bowel disease.

Proteins of the TFF family are characterized by obtaining a minimum of 1 copy of the trefoil motif, a 40-amino acid domain that contains 3 conserved disulfides. Trefoil Factors are stable secretory proteins expressed in gastrointestinal mucosa which protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium.TFF2 inhibits gastric acid motility & secretion. TFF2 stabilizes glycoproteins in the mucus gel through interactions with carbohydrate side chains. TFF3 induces ciliogenesis and promotes airway epithelial ciliated cell differentiation, relatively through an epidermal growth factor receptor-dependent pathway. TFF3 overexpression is crucial for progression in mouse and human hepatocellular carcinogenesis. TFF-3 is normally expressed in hepatocellular carcinoma and its expression associates with tumor grade.

The Trefoil Factor peptides (TFF1, TFF2 and TFF3) are stable secretory proteins expressed in the gastrointestinal tract (gastric mucosa), and are involved in intestinal mucosal defense and repair. TFF1 is an essential protein for normal differentiation of the antral and pyloric gastric mucosa and functions as a gastric-specific tumor suppressor gene. TFF1 is a stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. TFF1 protects the mucosa from isults, stabilizes the mucus layer, & affects healing of the epithelium. TFF1 is commonly expressed in tumors. TFF1 is related with the cell membrane of MCF-7 cells. High levels of TFF1 and TFF2 are found in serum from inflammatory bowel disease.

CD27 belongs to the TNF-receptor superfamily. CD27 is necessary for initiation and long-term maintenance of T cell immunity. CD27 binds to ligand CD70, and has a crucial role in regulating B-cell activation and immunoglobulin synthesis. The CD27 receptor transduces signals which result in the activation of NF-kappaB and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 mediate the signaling process of CD27. CD27-binding protein (SIVA), which is a proapoptotic protein, can bind to the CD27 receptor and is believed to have a significant role in the apoptosis induced by CD27.

Proteasome assembly chaperone 2 (PSMG2) stimulates assembly of the 20S proteasome as part of a heterodimer with PSMG1. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits and promotes compilation of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization. PSMG2 is widely expressed with highest levels in the lung, brain and colon. It is moderately expressed in the muscle, stomach, spleen and heart, and weakly expressed in the small intestine, pancreas and liver. It is also highly expressed in hepatocellular carcinomas with low levels in surrounding liver tissue.

Osteoprotegerin acts as decoy receptor for rankl and thereby neutralizes its function in osteoclastogenesis. OPG inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local rankl/opg ratio. Osteoprotegerin may also play a role in preventing arterial calcification. May act as decoy receptor for trail and protect against apoptosis. Trail binding blocks the inhibition of osteoclastogenesis.

Proteins of the TFF family are characterized by obtaining a minimum of 1 copy of the trefoil motif, a 40-amino acid domain that contains 3 conserved disulfides. Trefoil Factors are stable secretory proteins expressed in gastrointestinal mucosa which protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium.TFF2 inhibits gastric acid motility & secretion. TFF2 stabilizes glycoproteins in the mucus gel through interactions with carbohydrate side chains. TFF3 induces ciliogenesis and promotes airway epithelial ciliated cell differentiation, relatively through an epidermal growth factor receptor-dependent pathway. TFF3 overexpression is crucial for progression in mouse and human hepatocellular carcinogenesis. TFF-3 is normally expressed in hepatocellular carcinoma and its expression associates with tumor grade.

TRAF2 protein is related with transduce signals from members of the TNFR superfamily. TRAF2 is located in the cytoplasm binds to TRAF1, TRAF2, or TRAF3, thus inhibiting TRAF function by sequestering the TRAFs in a suppressed state in the cytoplasm. Overexpression of TANK inhibits TRAF2-mediated NF-Kappa-B activation signaled by CD40 and both TNF receptors and inhibits LMP1-mediated NF-kappa-B activation by blocking the association of TRAF2 with LMP1. TRAF2 is necessary for the cellular response to TNF-alpha by connecting upstream signalling molecules to the IKKs and p65.

OSTF1 is an intracellular protein produced by osteoclasts that induces bone resorption, via signaling cascade which results in the secretion of factors enhancing osteoclast formation and activity.

EFNA1 belongs to the ephrin (EPH) family. The EPH subfamily is the biggest group of receptor protein kinases and they take part in vital nervous system function and development.

CD40L or CD154 is a membrane glycoprotein and differentiation antigen expressed on the surface of T-cells. The CD40 ligand stimulates B-cell proliferation and secretion of all immunoglobulin isotypes in the presence of cytokines . CD40 ligand has been shown to induce cytokine production and tumoricidal activity in peripheral blood monocytes. It also costimulates proliferation of activated T-cells and this is accompanied by the production of IFN-gamma , TNF-alpha , and IL2.

CD40L or CD154 is a membrane glycoprotein and differentiation antigen expressed on the surface of T-cells. The CD40 ligand stimulates B-cell proliferation and secretion of all immunoglobulin isotypes in the presence of cytokines . CD40 ligand has been shown to induce cytokine production and tumoricidal activity in peripheral blood monocytes. It also costimulates proliferation of activated T-cells and this is accompanied by the production of IFN-gamma , TNF-alpha , and IL2 .