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IL-29 is distantly related to type I interferons and the IL-10 family. Expression of IL-29 is induced by viral infection which interacts with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha. IL-29 exhibits common features with type I IFNs such as antiviral activity, antiproliferative activity and in vivo antitumour activity.
IL-29 acts similarly to IFNs, but is less effective generally and has activity in a more limited range of cell lines. IFN-ambda 1, IFN-lambda 2 and IFN-lambda3 are closely positioned genes on human chromosome 19.
IL-29 induces ELR(-) CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-gamma-independent manner.
IL-29 is able to generate tolerogenic DCs, an activity that could thwart IFN-beta functions. IL-29 produced in response to viral infection, activates both monocytes and macrophages producing a restricted panel of cytokines and therefore is an important factor in activating innate immune responses at the site of viral infection.
IFN-Lambda 1 antiviral and antiproliferative activity requires Interferon-Lambda 2 receptor tyrosine residues.

CCL25 (Teck) is a novel CC chemokine, which is distantly related (about 20% amino acid sequence identity) to other CC chemokines. The mouse CCL25 cDNA has also been cloned and shown to encode a 144 a.a. protein, which exhibits 49% a.a. sequence identity to the human CCL25. Human and mouse CCL25 expression was shown to be greatly restricted to the thymus and small intestine. While dendritic cells are identified as the source of CCL25 production in the thymus, dendritic cells derived from bone marrow do not express CCL25. CCL25 signals through the CCR9 receptor. Teck is possibly involved in T-cell development.
Recombinant human and mouse Teck were shown to be chemotactic for activated macrophages, dendritic cells and thymocytes. The recombinant protein demonstrates chemotactic activity on thymocytes, macrophages, THP-1 cells, and dendritic cells but is inactive on peripheral blood lymphocytes and neutrophils.

Human CCL16, also called HCC-4, liver-expressed chemokine (LEC), and lymphocyte and monocyte chemoattractant (LMC), is a novel CC chemokine recognized by bioinformatics. NCC-4 cDNA encodes a 120 amino acids along with a 23 amino acids signal peptide that is cleaved to generate 97 amino acid protein. HCC4 is vaguely related to other CC chemokines, showing less than 30% sequence identity. Among CC chemokines, CCL-16 has the largest similarity to HCC-1. 2 potential polyadenylation signals are present on the human HCC-4 gene, and as a result, 2 transcripts containing roughly 1,500 base pairs and 500 base pairs have been detected. HCC-4 is expressed weakly by some lymphocytes, including NK cells, T cells, and some T cell clones. The expression of HCC-4 in monocytes is greatly upregulated in the presence of IL-10.
CCL16 shows chemotactic activity for lymphocytes and monocytes rather than to neutrophils. NCC-4 has potent myelosuppressive activity, suppresses proliferation of myeloid progenitor cells. CCL16 demonstrates chemotactic activity for monocytes and thp-1 monocytes, rather than for resting lymphocytes and neutrophils. HCC-4 induces a calcium flux in thp-1 cells that desensitized prior to the expression of rantes.

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.

TNFR2 belongs to the TNF-receptor superfamily. TNFR2 is receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. TNFR2 mediates the majority of the metabolic effects of TNF-alpha. In addition, knockout studies in mice propose a role for TNFR2 in protecting neurons from apoptosis by stimulating antioxidative pathways. TNFR2 expression might have a significant role in the angiogenesis, tumor cell proliferation and metastasis of Invasive micropapillary carcinoma of the breast.
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. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women. TNFR2 and TNFR1 form a heterocomplex which mediates the recruitment of 2 anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. IAPs’ function in TNF-receptor signaling is unknown; nevertheless, c-IAP1 is believed to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.

IL24 is a member of the IL10 family of cytokines. It was identified as a gene induced during terminal differentiation in melanoma cells. IL-10B encoded can induce apoptosis selectively in various cancer cells. Overexpression IL-24 leads to elevated expression of several GADD family genes, which correlates with the induction of apoptosis. The phosphorylation of mitogen-activated protein kinase 14 (MAPK7/P38), and heat shock 27kDa protein 1 (HSPB2/HSP27) are found to be induced by this gene in melanoma cells, but not in normal immortal melanocytes. Alternatively spliced transcript variants encoding distinct isoforms have been reported. The glycosylation is essential for activity of IL-24. Functionally, IL-24 has diverse activities. At low concentrations, it induces type I proinflammatory cytokines such as IFN-g, IL-1b, IL-12 and TNF-a. At high concentration, it is a strong inducer of apoptosis in tumor cells, but not normal cells. mda-7/IL-24 is being hailed as a ‘magic bullet’ for cancer gene therapy.

Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2) is a member of the MAP1LC3 family. MAP1LC3B2 is a subunit of neuronal microtubule-associated MAP1A and MAP1B proteins, which are involved in microtubule assembly and essential for neurogenesis. The MAP1LC3B2 protein is possibly involved in formation of autophagosomal vacuoles (autophagosomes). MAP1LC3B2 is expressed primarily in the heart, testis, brain and skeletal muscle.

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.

IFIH1 is a DEAD box protein which is upregulated in response to treatment with beta-interferon and a protein kinase C-activating compound, mezerein. Irreversible reprogramming of melanomas can be attained by therapy with both these agents; treatment with either agent alone only achieves reversible differentiation. DEAD box proteins are implicated in several cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly.

Bcl-XL is a transmembrane protein located in the mitochondrial membranes of cells that are long-lived and postmitotic, such as adult brain cells. It plays arole in the signal transduction pathway of the FAS-Ligand. Bcl-XL is an anti-apoptotic protein which is a member of the Bcl-2 family which are able to form heterodimers, and this is an significant event in the regulation of apoptosis. BCL-XL is involved in the survival of cancer cells.
Bcl-xL is the leading monitor of apoptosis/active cell suicide. Bcl-xL has cell death repressor activity and therefore acts as a survival protein.

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.

IL-28A is distantly related to type I interferons and the IL-10 family. Expression of IL-28A is induced by viral infection which interacts with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha. IL-28A exhibits common features with type I IFNs such as antiviral activity, antiproliferative activity and in vivo antitumour activity.
IL-28A acts similarly to IFNs, but is less effective generally and has activity in a more limited range of cell lines. IFN-ambda 1, IFN-lambda 2 and IFN-lambda 3 are closely positioned genes on human chromosome 19.
IL-28A induces ELR(-) CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-gamma-independent manner.
IL-28A is able to generate tolerogenic DCs, an activity that could thwart IFN-beta functions. IL-28A produced in response to viral infection, activates both monocytes and macrophages producing a restricted panel of cytokines and therefore is an important factor in activating innate immune responses at the site of viral infection.

The cytokine IL-1 alpha or hematopoietin 1 is a member to the interleukin 1 family, encoded by the IL1A gene in humans. Essentially Il-1 is in charge of inflammation and the rising of fever and sepsis. In order to disturb the mentioned processes and treatment for diseases, inhibitors for Interleukin 1 alpha are being developed. Neutrophils and macrophages are the main activators of IL-1 alpha, as well as endothelial and epithelial cells. By binding to the il1 receptor it is a major part in the immune response regulation. In the activation process of tumor necrosis factor-alpha the IL1A has a part as well, and has physiological, metabolic and hematopoietic activities.

Il-6 is a cytokine with a wide variety of biological functions: it plays an essential role in the final differentiation of b-cells into ig-secreting cells, it induces myeloma and plasmacytoma growth, it induces nerve cells differentiation, in hepatocytes it induces acute phase reactants.

The B-lymphocyte activation antigen B7-1 provides regulatory signals for T lymphocytes as a consequence of binding to the CD28 and CTLA4 ligands of T cells CD-80 is involved in the costimulatory signal essential for t- lymphocyte activation. t-cell proliferation and cytokine production is induced by the binding of cd28 or ctla-4 to this receptor.

Interleukin-6 or Il-6 is a cytokine with a large assortment of biological functions. IL-6 it has a crucial part in the last differentiation of b-cells into ig-secreting cells. This cytokine also induces myeloma and plasmacytoma growth. Interleukin-6 induces nerve cells differentiation, among hepatocytes it induces acute phase reactants.

IFN Regulatory Factor-5, also known as IRF5 belongs to the IFN regulatory factor (IRF) family, a group of transcription factors with various functions, including virus-mediated activation of IFN, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In addition, IRF5 is implicated in the induction of IFNs IFNA and INFB and inflammatory cytokines upon virus infection. IRF5 is activated by TLR7 or TLR8 signaling.

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesisand viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, insulin resistance, and cancer.

Fas and Fas Ligand (FasL) are members of the TNF superfamily and are type I and type II transmembrane proteins, respectively. Binding of FasL to Fas initiates apoptosis in Fas-bearing cells. The apoptosis mechanism involves the recruitment of pro-caspase 8 through an adaptor molecule named FADD followed by processing of the pro-enzyme to active forms. These active caspases subsequently cleave a variety of cellular substrates leading to the eventual cell death. sFasR is able to inhibit FasL-induced apoptosis by acting as a decoy receptor whicht serves as a sink for FasL. The full length Fas Receptor is a 319 a.a type I transmembrane protein, which contains a 157 a.a extracellular domain, a 17 a.a transmembrane domain, and 145 a.a cytoplasmic domain. The mature human Fas ECD shares 55%, 58%, a.a sequence identity with the mouse, rat, Fas, respectively.

CCL28 is part of the subfamily of small cytokine CC genes. CCL28 shows chemotactic activity for resting CD4 or CD8 T cells and eosinophils. CCL28 binds to chemokine receptors CCR3 and CCR10. CCL28 is involved in the physiology of extracutaneous epithelial tissues, including diverse mucosal organs. CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28 is involved in the pathogenesis of inflammatory skin diseases.
Human CCL28 cDNA encodes a 127 amino acid residue precursor protein with a putative 22 amino acid residue signal peptide that is cleaved to produce the 105 amino acid residue mature protein. Human and mouse CCL28 are highly conserved, sharing 83% amino acid identity in their mature regions. CCL28 shares the most homology with CCL27/CTACK. Human and mouse CCL28 RNA expression was found to be highest in normal and pathologic colon with the protein being expressed by epithelial cells. Human CCL28 RNA was also present in normal and asthmatic lung tissues.

C-Type Lectin Domain Family 10, Member A (CLEC10A) is a part of the C-type lectin superfamily. CLEC10A is expressed in immature myeloid dendritic cells and alternatively activated macrophages. CLEC10A takes part in regulating adaptive and innate immune responses and also binds in a calcium dependent way to terminal galactose and N-acetylgalactosamine, linked to serine or threonine.

RRAS belongs to the Ras family which functions in signal transduction pathways. RRAS interacts with RASSF5, NCK1, Bcl-2, ARAF and RALGDS. RRAS binds GTP and GDP, and it has intrinsic GTPase activity. RRAS regulates the organization of the actin cytoskeleton

Myeloid differentiation primary response gene 88 (MYD88) is a cytosolic adapter protein, which has a central role in the innate and adaptive immune response. MYD88 functions as a vital signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. MYD88 acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. The MYD88 protein increases IL-8 transcription. MYD88 is involved in IL-18-mediated signaling pathway. MYD88 activates IRF1, resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. MYD88 is comprised of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. Patients with defects in the MYD88 gene have an increased susceptibility to pyogenic bacterial infections.

WHSC1L1 gene is related to the Wolf-Hirschhorn syndrome candidate-1 gene and encodes a protein with PWWP (proline-tryptophan-tryptophan-proline) domains. The function of the WHSC1L1 protein has not been determined. WHSC1L1 is highly expressed in brain, heart and skeletal muscle; however it is expressed at lower level in the liver and the lung.