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Chemokine (C-X-C motif) ligand (CXCL7) is a small cytokine belonging to the CXC chemokine family. It is a protein that is released in large amounts from platelets following their activation. It stimulates various processes including mitogenesis, synthesis of extracellular matrix, glucose metabolism and synthesis of plasminogen activator.

Interleukin-1 ra is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interaction plays an important role in the immune system and lack of this system leads to autoimmunity, indicating that Fas-mediated apoptosis removes self-reactive lymphocytes. Fas signaling is also involved in immune surveillance to remove transformed cells and virus infected cells. Binding of FAS to oligimerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are first activated, to then cleave and activate downstream caspases, and a variety of cellular substrates that lead to cell death. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure and another caspase substrate is DFF, inducing cleavage and degradation of the genome. Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. Activation of JNK kinase, activation of Jun, and production of ceramide may also play roles in Fas-mediated apoptosis. Activation of fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and tumors may escape immune surveillance in part through suppression of fas-mediated apoptosis using similar mechanisms.

Caspase 3 Apoptosis-Related Cysteine Peptidase (CASP3) belongs to the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a key role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to generate 2 subunits, large and small, that dimerize to create the active enzyme. CASP3 protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. CASP3 is the leading caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is linked with neuronal death in Alzheimer's disease. In addition, CASP3 is involved in the cleavage of huntingtin. CASP3 also cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. CASP3 initiates cell adhesion in sympathetic neurons through RET cleavage.

Macrophage Inflammatory Proteins belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1a and MIP-1b that are now also named CCL3 and CCL4. Both factors are produced by macrophages after they are stimulated with bacterial endotoxins. MIP-1a and MIP-1b activate human granulocytes (neutrophils, eosinophils and basophils) which can lead to acute neutrophilic inflammation. MIP-1a and MIP-1b induce synthesis and release of other pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6 and TNF-alpha from fibroblasts and macrophages. CCL3 and CCL4 genes are both located on human chromosome 17.

Interleukin-1 ra is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

IL-25 also called IL-17E cytokine has a sequence similarity with IL17.
IL-17E indluces NF-kappaB activation, and stimulates the production of IL-8. IL17E and IL17B are ligands for the cytokine receptor IL17BR. IL-25 is a proinflammatory cytokine favoring Th2-type immune response. The upregulation of costimulation-induced IL-17E receptors and release of cytokines and chemokines from IL-17E treated costimulated Th cells are differentially regulated by intracellular JNK, p38 MAPK and NF-kappaB activity. Blocking Iinterleukin-25 prevents airway hyperresponsiveness, a critical feature of clinical asthma. IL25 produced by innate effector eosinophils and basophils increase the allergic inflammation by enhancing the maintenance and functions of TSLP-DC activated adaptive Th2 memory cells. Over expression of IL-25 up-regulates gene expression of Th2 cytokines and induces growth retardation, jaundice, and multiorgan inflammation in a transgenic mouse model. IL-25 contributes to the induction and maintenance of eosinophilic inflammation by acting on lung fibroblasts which supports the fact that IL-17E is an important factor in asthma pathophysiology. IL-17E operates by amplifying TH2 cell-mediated allergic airway inflammation but doesn’t induce allergic inflammation in vivo.

TARC cDNA encodes a 94 amino acid precursor protein with a 23 amino acid residue signal peptide that is cleaved off to generate the 71 amino acid residue mature secreted protein. Along with CC chemokine family members, CCL-17 has approximately 24-29% amino acid sequence identity with RANTES, MIP-1a, MIP-1b, MCP-1, MCP-2, MCP-3 and I-309. TARC is expressed in thymus, and at a lower level in the lung, colon, and small intestine. TARC is in addition transiently expressed in stimulated peripheral blood mononuclear cells. Recombinant TARC has been shown to be chemotactic for T cell lines but not monocytes or neutrophils. CCL-17 was recently identified to be a specific functional ligand for CCR4, a receptor that is selectively expressed on T cells. CCL17 is one of quite a few Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. CCL17 shows chemotactic activity for T lymphocytes, but not monocytes or granulocytes. CCL17 binds to chemokine receptors CCR4 and CCR8. This chemokine plays important roles in T cell development in thymus as well as in trafficking and activation of mature T cells.

TNFR1 belongs to the TNF-receptor superfamily. TNFR1 is a receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.
TNFR1 is capable of signaling both cell survival and apoptosis. TNFR1-induced apoptosis requires 2 sequential signaling complexes. TNFR1 is capable of activating NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNFR1 contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Human TNFR1 has a major region which controls cell surface expression. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women.
Germline mutations of the extracellular domains of TNFR1 are linked to the autosomal dominant periodic fever syndrome. The impaired receptor clearance is believed to be a mechanism of the disease. Familial hibernian fever (FHF) is caused by defects in TNFRSF1A gene.

Myxovirus Resistance 1, also known as MX1 is a guanosine triphosphate (GTP)-metabolizing protein which takes part in the cellular antiviral response. MX1 is induced by type I and type II IFN, and also antagonizes the replication process of some different RNA & DNA viruses. In addition, there is a related gene located adjacent to MX1 on chromosome 21, and there are multiple pseudogenes positioned in a cluster on chromosome 4.

IFNs are cytokines that are widely known to induce potent anti-viral activity. IFN-a exerts a variety of other biological effects, including antitumor and immunomodulatory activities and are increasingly used clinically to treat a range of malignancies, myelodysplasias and autoimmune diseases.

IFN alpha 7 (IFNA7) is a member of the alpha/beta IFN family. IFNA7 is generated by macrophages. IFN-alpha has antiviral functions. IFN promotes the production of 2 enzymes: a protein kinase and an oligoadenylate synthetase.

Interleukin-1b is produced by activated macrophages, IL-1B stimulates thymocyte proliferation by inducing il-2 release, b-cell maturation and proliferation, and fibroblast growth factor activity. IL1B proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin from synovial cells.

IL10 is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract.

Active IL-12 is a p70 disulphide-linked dimer composed of p35 and p40 subunits. The protein is a pleiotropic cytokine produced primarily by antigen presenting cells and has multiple effects on T lymphocytes and natural killer cells in terms of stimulating cytotoxicity, proliferation, production of other cytokines and Th1 subset differentiation.

IL-31 produced by activated Th2-type T cells, cooperates with a heterodimeric receptor consisting of IL-31 Receptor Anatagonist and Onconstatin-M Receptor that is continuesly expressed on epithelial cells and keratinocytes. IL-31 plays a role in the promotion of allergic skin disorders and in regulating other allergic diseases, such as asthma. IL-31 is involved in the itching sensation and endorses the scratching behavior in NC/Nga mice with atopic dermatitis. IL-31 expression is connectd with CLA(+) T cells and contributes to the development of atopic dermatitis-induced skin inflammation and pruritus. IL-31 is a powerful inducer of proinflammatory mediators in human colonic SEMFs. IL-31 takes part as a proinflammatory cytokine derived from Th2 cells.
Serum IL-31 level is higher in patients with atopic dermatitis. IL-31 is involved in a broad range of immune- & non-immune cells & possesses potential pleiotropic physiological functions, including regulating hematopoiesis & immune response, causing inflammatory bowel disease, airway hypersensitivity & dermatitis.

IL4 is a pleiotropic cytokine produced by activated T cells. IL4 is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. IL4, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

Interleukin-1 ra is a member of the interleukin 1 cytokine family. IL1RAinhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. IL1RAand five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer.

Murine IL-36a belongs to the IL-1 family that includes IL-1b, IL-1a, IL-1ra, IL-18, IL-36ra (IL1F5), IL-36b (IL1F8), IL-36g (IL1F9), IL-37 (IL1F7) and IL-38 (IL-1F10). The IL-1 family members display a 12 b-strand, b-trefoil configuration, and are thought to have ascended from a mutual ancestral gene. Murine IL-36a is a 160 amino acid intracellular and secreted protein which holds no signal sequence, no prosegment and no potential N-linked glycosylation sites. IL-36a is released as a reaction to LPS and the cell ATP-induced activation of the P2X7 receptor.
Mouse to human, full length IL-36a/IL-1F6 shares 54% aa sequence homology. IL-36a is mostly found in skin and lymphoid tissues, but also in fetal brain, trachea, stomach and intestine.

CD276, belongs to the B7 family of immunoregulatory transmembrane glycoproteins expressed by T cells. CD276 is a costimulatory molecule for T cell activation in addition to IFN-gamma production. Furthermore CD276 upregulates BRCC3 expression, preventing DNA defects caused by 5-Fu. CD276 is correlated with TNM stage of NSCLC and act as a potential biomarker for NSCLC-derived MPEs. CD276 inhibits natural-killer mediated cell lysis in tumor cells, and act as a marker for detection of neuroblastoma cells. CD276 is implicated in the development of acute as well as chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. In addition, CD276 provides the placenta & fetus a proper immunological environment during the course of pregnancy.

Leukocyte Cell-Derived Chemotaxin 2 (LECT2) functions as a chemotactic factor to neutrophils. LECT2 stimulates the proliferation of chondrocytes and osteoblasts. LECT2 is strongly expressed in the liver and weakly in the testis. LECT2 is a secreted, 16kDa protein which serves as a chemotactic factor to neutrophils and stimulates the growth of chondrocytes and osteoblasts. LECT2 protein has a high sequence similarity to the chondromodulin repeat regions of the chicken myb-induced myeloid 1 protein. A polymorphism in the LECT2 gene is linked with rheumatoid arthritis.

UPK3A is a member of the uroplakin-3 family. Uroplakins (UP) which are transmembrane proteins are important components of the urothelium that pass the lipid bilayer once (UPII, UPIIIa, and UPIIIb) or four times (UPIa and UPIb; both members of the "tetraspanin" family). All hold great luminal/extracellular domains, but only UPIIIa and UPIIIb have significant cytoplasmic shares in their C-termini. UPK3A is an extremely specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas. Alterations in this gene are related to renal adysplasia.

IL17 is a proinflammatory cytokine produced by activated T cells. IL-17 regulates the activities of NF-kappaB and mitogen-activated protein kinases. Interleukin-17 can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). High levels of IL-17 are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis.