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Resistin, a product of the RSTN gene, is a peptide hormone belonging to the class of cysteine-rich secreted proteins which is termed the RELM family, and is also described as ADSF (Adipose Tissue- Specific Secretory Factor) and FIZZ3 (Found in Inflammatory Zone). Human resistin contains 108 amino acids as a prepeptide, and its hydrofobic signal peptide is cleaved before its secretion. Resistin circulates in human blood as a dimeric protein consisting of two 92 amino acid polypeptides, which are disulfide-linked via Cys26.
Resistin may be an important link between obesity resistance. Mouse resistin, specifically produced and secreted by adipocyte, acts on skeletal muscle myocytes, hepatocytes and adipocytes themselves so that it reduces their sensitivity. They have also suggested that resistin is present at elevated levels in blood of obese mice, and is down regulated by fasting and antidiabetic drugs. Way et al., on the other hand, have found that resistin expression is severly suppressed in obesity and is stimulated by several antidiabetic drugs.
Other studies have shown that mouse resistin increases during the differentiation of adipocytes, but it also seems to inhibit adipogenesis. In contrast, the human adipogenic differentiation is likely to be associated with a down regulation of resistin gene expression.

Uteroglobin (SCGB1A1) which belongs to the Secretoglobin (SCGBs) superfamily, is a multifunctional protein that exerts anti-inflammatory and anti-tumorigenic effects by binding small hydrophobic molecules such as phospholipids and prostaglandins. Uteroglobin is involved in numerous functions including anti-inflammation, inhibition of phospholipase A2 and the sequestering of hydrophobic ligands. SCGB1A1 is expressed by Clara cells, the non-ciliated, non-mucous secretory cells predominant in lung bronchioles, and by other epithelia which communicate with the external environment. On top of sequestering pro-inflammatory mediators and carcinogens, Uteroglobin is implicated in the inhibition of cell migration and invasion, platelet aggregation, and T cell differentiation. SCGB1A1 gene defects are associated with a susceptibility to asthma.

FLT3 ligand is a receptor for the fl cytokine has a tyrosine-protein kinase activity & a growth factor that regulates proliferation of early hematopoietic cells. Flt3-Ligand synergizes with other CSFs and interleukins to induce growth and differentiation.

Chemokine (C-X-C motif) ligand 5 (CXCL5) is a small cytokine belonging to the CXC chemokine family that is also known as epithelial-derived neutrophil-activating peptide 78 (ENA-78). It is produced following stimulation of cells with the inflammatory cytokines interleukin-1 or tumor necrosis factor-alpha. Expression of CXCL5 has also been observed in eosinophils. This chemokine stimulates the chemotaxis of neutrophils possesses angiogenic properties. It elicits these effects by interacting with the cell surface chemokine receptor CXCR2. The gene for CXCL5 is encoded on four exons and is located on human chromosome 4 amongst several other CXC chemokine genes. CXCL5 has been implicated in connective tissue remodelling.

A fusion tag called FLAG consists of eight amino acids (AspTyrLysAspAspAspAspLys) including an enterokinase-cleavage site. FLAG is specifically designed for immunoaffinity chromatography. It allows elution under non-denaturing conditions. Several antibodies against this peptide have been developed. One antibody denoted as M1 binds the peptide in the presence of bivalent metal cations preferably Ca(+). Elution is effected by chelating agents. Another strategy is competitive elution with excess of free Flag Peptide. The FLAG peptide purifies and detects recombinant fusion proteins. FLAG peptide is useful in Western blotting, immunocytochemistry, immunoprecipitation, flow cytometry, protein purification, and in the study of protein-protein interactions, cell ultrastructure, and protein localization. Flag peptide is a hydrophilic tag which significantly improves the detection and purification of recombinant fusion proteins.

Adiponectin is an adipocyte specific secreted protein that circulates in the plasma. It is induced during adipocyte differentiation and its secretion is stimulated by insulin. Mouse adiponectin shares about 83% amino acid identity with that human. Adiponectin plays a role in various physiological processes such as energy homeostasis and obesity. Adiponectin is reduced in obese humans, and decreased level is associated with insulin resistance and hyperinsulinemia.

Basic fibroblast growth factor is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Three alternatively spliced variants encoding different isoforms have been described. The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.

CCL-20 is a chemotactic factor that draws lymphocytes & neutrophils, rathar than monocytes. MIP-3 alpha inhibits proliferation of myeloid progenitors in colony formation assays. MIP3A plays a role in the formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. CCL-20 holdes antibacterial activity e.coli atcc 25922 and s.aureus atcc 29213. CCL-20 gene transcription is activated by H. pylori, which activates NF-kappaB through intracellular signal pathway which involves IkappaB kinase and NF-kappaB-inducing kinase. MIP-3 alpha is invloved in chemokine-mediated lymphocyte trafficking during gastric inflammation in Helicobacter infection. CCL-20 expression is involved in the recruitment of CD45R0-positive T cell subsets into the intestinal lamina propria. MIP-3A is in charge of the advancement of pulpal inflammation through the recruitment of C-C motif Receptor 6-expressing lymphocytes Vaginal epithelial cells respond to factors present in semen by secreting MIP-3 alpha, which increases langerhans cells recruitment during HIV transmission.

Chromosome 10 Open Reading Frame 54, also known as C10ORF54 is part of the immunoglobulin superfamily. Like a transmembrane molecule, C10ORF54 is expressed in the bone on embryonic stem cells (ESCs), and on tumor cell surface as well. Accordingly, C10ORF54 supports the differentiation of ESC and ehhances BMP4 induced signaling in ESC, however C10ORF54 is also down regulated following to BMP4 exposure.

FAS or tumor necrosis factor receptor superfamily member 6 or TNFRSF6, is part of the death receptor family, which is part of the TNF receptor protein family. TNFRSF6 has a crucial part in regulating viral infections. FAS protein can be found in almost all cell types, when its cognate ligand (FasL) can be found in activated T cells, NK cells & dendritic cells. The regulating protein of FasL & TRAIL on HCMV-infected dendritic enhances direct destruction of activated T lymphocytes. furthermore, subvertneutrophil function in HCMV retinitis can occur when FasL is activated in HCMV infected retinal pigment epithelial cells.

Thrombopoietin is a glycoprotein hormone produced mainly by the liver and the kidney that regulates the production of platelets by the bone marrow. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets.

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid. CXCL12 is strongly chemotactic for lymphocytes and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

The type II transmembrane protein FASLG is a member of the tumor necrosis factor (TNF) superfamily. A fas ligand/receptor interaction has a significant part in the regulation of the immune system and the advancement of cancer. FASLG is expressed on the activated T cell surface as a nondisulfidelinked homotrimer. FASLG binding to Fas/CD95/TNFRSF6 on a nearby cell prompts apoptosis in the Fas expressing cell. FASLG is released from the cell surface by metalloproteinases as a soluble molecule that stays trimeric and is able to bind with Fas, but its capability to activate apoptosis is radically reduced. In addition, FASLG binds to DcR3 - a soluble trap receptor with no signal transduction capabilities. Flawed Fas-mediated apoptosis causes oncogenesis in addition to drug resistance in existing tumors. Constitutive expression of FASLG in a variety of tumors enables their immune evasion. Both mouse and human FASLG are active on mouse and human cells.

Janus Kinase 2 (JAK2) is a protein tyrosine kinase which takes part in a specific subset of cytokine receptor signaling pathways such as cell growth, development, differentiation or histone modifications. JAK2 is linked with the prolactin receptor and is necessary for responses to gamma IFN. Mice which do not express an active protein for JAK2 show embryonic lethality associated with the absence of definitive erythropoiesis.

MDC (CCL22) is a small cytokine that belongs to the CC chemokine family. CCL22 is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. MDC shows chemotactic activity for natural killer cells, chronically activated T lymphocytes, monocytes and dendritic cells. On the other hand, MDC shows a mild activity for primary activated T lymphocytes and has no chemoattractant activity for neutrophils, eosinophils and resting T lymphocytes. MDC may also have a role in the trafficking of activated T lymphocytes to inflammatory sites and other aspects of activated T lymphocyte physiology. MDC interacts with cell surface chemokine receptors CCR4.
CCL22 is vastly expressed in macrophage and in monocyte-derived dendritic cells, and thymus. CCL22 is also found in the lymph node, appendix, activated monocytes, resting and activated macrophages. Lower expression of CCL22 can be seen in the lung and the spleen and very weak expression in the small intestine. In the lymph node CCL22 is expressed in a mature subset of Langerhans' cells (CD1a+ and CD83+).
Furthermore, CCL22 is expressed in atopic dermatitis, allergic contact dermatitis skin, and psoriasis, in both the epidermis and dermis. In addition, MDC has a role in hindering progression of lung cancer. Moreover, significantly higher CCL22 expression is linked to gastric cancer.

RELM-beta (Resistin-Like Molecule-beta) is a member of a recently identified family of secreted proteins containing a conserved cystein-rich C-terminus. The RELM family consists of resistin (also called FIZZ3), RELM-alfa (FIZZ1), RELM-beta (FIZZ2) and RELM-gamma. Only resisistin and RELM-beta were found in humans whereas all four RELM family members were identified in rodents.
RELM-beta appears to be produced as a homodimer exclusively by intestinal goblet cells and can be found in high quantities in stool. Remarkably, stool of germ-free mice displaying sterile intestinal tract does not contain RELM-beta until bacterial colonization takes place after pathogen-free mice entered natural environment. Some, but not all, colon carcinoma cell lines secrete RELM-beta into the cell culture supernatant.
The physiological function of RELM-beta is not known. High doses of recombinant RELM-beta showed hyperglycemic effects including lowered glucose disposal and increased hepatic glucose production in mice.

Uteroglobin (SCGB1A1) which belongs to the Secretoglobin (SCGBs) superfamily, is a multifunctional protein that exerts anti-inflammatory and anti-tumorigenic effects by binding small hydrophobic molecules such as phospholipids and prostaglandins. Uteroglobin is involved in numerous functions including anti-inflammation, inhibition of phospholipase A2 and the sequestering of hydrophobic ligands. SCGB1A1 is expressed by Clara cells, the non-ciliated, non-mucous secretory cells predominant in lung bronchioles, and by other epithelia which communicate with the external environment. On top of sequestering pro-inflammatory mediators and carcinogens, Uteroglobin is implicated in the inhibition of cell migration and invasion, platelet aggregation, and T cell differentiation. SCGB1A1 gene defects are associated with a susceptibility to asthma.

Suppressor of IKBKE 1 also known as SIKE1 belongs to the SIKE family. SIKE interacts with IKK-epsilon and TBK1 and function as a suppressor of TLR3. In addition, SIKE1 perform by disrupting the interactions of IKBKE or TBK1 with TICAM1/TRIF, IRF3 andDDX58/RIG-I. SIKE1 does not inhibit NF-kappa-B activation pathways.

ITGB4 (integrin beta-4 isoform 1) belongs to the Integrin beta family. ITGB4 forms noncovalent heterodimers with Integrin alpha 6 and takes part in the formation of epithelial hemidesmosomes. ITGB4 has a vital structural role in the hemidesmosome of epithelial cells and is needed for the regulation of keratinocyte motility & polarity. ITGB4 leans towards the association with alpha 6 subunit and is expected to take a key role in the biology of invasive carcinoma.

Glia Maturation Factor-Beta (GMF-Beta) is a 17 kDa protein nerve gorwth factor identified as a growth and differentiation factor in the vertebrate brain.

Glia Maturation Factor-Beta stimulates differentiation of normal neurons as well as glial cells. GMFB inhibits the proliferation of the N-18 neuroblastoma line and the C6 glioma line while promoting their phenotypic expression.
GMF-beta inhances the phenotypic expression of glia & neurons thus inhibits the proliferation of their respective tumors when added to cell culture. Although astrocytes produce GMF-b and stores it inside the cells, they don’t secrete the GMF-B into the cultured medium. Cell- surface GMFb acts on the target cells at close range when cells are in direct contact. GMF-Beta is produced by thymic epithelial cells and plays an important role in T cell development in favor of CD4+ T cells.
GMF-Beta is a brain-specific protein which belongs to the actin-binding proteins (ADF) family. GMF-beta appears to play a role in the differentiation, maintenance, and regeneration of the nervous system. It also supports the progression of certain auto-immune diseases, possibly through its ability to induce the production and secretion of various pro-inflammatory cytokines.

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.

B-Cell Maturation Antigen or TNFRSF17 or tumor necrosis factor receptor superfamily member 17, is part of the TNF receptor protein family. This protein is a TNFSF13B/BLyS/BAFF, TNFSF13/APRIL & promotes B-cell survival receptor. TNFRSF17 has a crucial part in the humoral immunity regulation. This protein is responsible for the activation of NF-kappa-B & JNK.