Interleukin 20 (IL20) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that is in

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

s encoded by the ''IL20''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

which is located in close proximity to the IL-10 gene on the 1q32

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...

. IL-20 is a part of an IL-20 subfamily which is a part of a larger

IL-10 family The IL10 family is a family of interleukins. In addition to IL-10, it includes IL-19, IL-20, IL-22, IL-24 and IL-26. Some sources also include the interferon Interferons (IFNs, ) are a group of signaling proteins made and released by ...

. IL-20 subfamily also includes other

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...

s, including IL-19, IL-20,

IL-22 Maltese ( mt, Malti, links=no, also ''L-Ilsien Malti'' or '), is a Semitic language derived from late medieval Sicilian Arabic with Romance superstrata spoken by the Maltese people. It is the national language of Malta and the only offici ...

, IL-24, and IL-26. Members of the

IL-20 subfamily form an important link between the immune system and epithelial tissues due to the fact that receptors for these

s are highly expressed on

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

and are almost exclusively produced by

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

of the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...

. IL-20 requires an IL-β-subunit receptor ( IL-20RB) for signaling, which can form a functional heterodimeric receptor with either the α-subunit of the IL-20 receptor (IL-20RA) or the α1-subunit of the IL-22 receptor (IL-22RA1). Both of these receptor variants allow efficient IL-20 signaling. Receptors for IL-20 are expressed in the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

, lungs,

ovary The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the bod ...

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...

, and

placenta The placenta is a temporary embryonic and later fetal organ (anatomy), organ that begins embryonic development, developing from the blastocyst shortly after implantation (embryology), implantation. It plays critical roles in facilitating nutrien ...

. IL-20 is mainly produced by

myeloid cells A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow (can be found in circulating blood when caused by certain diseases). Structure When stained with the usual dyes, the cytoplasm is distinctly basophilic ...

such as

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also i ...

granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ...

s, and

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

s but can also be produced by

keratinocyte Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referred ...

s and

fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of ...

s. The expression of IL-20 is stimulated by

IL-1β Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...

, IL-17,

, TNF, and

LPS LPS may refer to: Science and medicine * Lipopolysaccharide (Endotoxin) * Levator palpebrae superioris muscle Schools * Leighton Park School in Reading, England * Lexington Public Schools, a school district in Massachusetts, USA * Lincoln P ...

. The main cellular targets of IL-20 are

endothelial cells The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ves ...

, and

adipocyte Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesi ...

s. IL-20 has been shown to transduce its signal through signal transducer and activator of transcription 3 (

STAT3 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family. Function STAT3 is a member of the STAT protein family. In respo ...

) in

Function

IL-20 has a broad range of functions and is involved in a variety of immune and non-immune processes in the body. For example, IL-20 is involved in the process of

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier aga ...

, proliferation of

, prevention of apoptosis of

, regulation of differentiation of

s during

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

, the expansion of multipotential hematopoietic progenitor cells, and more. A specific receptor for this

is highly upregulated in psoriatic skin. Dysfunctional

regulation Regulation is the management of complex systems according to a set of rules and trends. In systems theory, these types of rules exist in various fields of biology Biology is the scientific study of life. It is a natural science with a ...

of IL-20 could lead to uncontrollable

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complet ...

, which could be a contributing factor to the pathogenesis of this disease. Because IL-20 is involved in the promotion of

proliferation Proliferation may refer to: Weapons *Nuclear proliferation, the spread of nuclear weapons, material, and technology *Chemical weapon proliferation, the spread of chemical weapons, material, and technology * Small arms proliferation, the spread of ...

it is also linked to the development of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

. Receptors for IL-20 are very often expressed on tumorous cells of

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

origin. High expression of IL-20 is also associated with

bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become ma ...

. On the other hand, IL-20 is known to prevent tissue damage as a result of chronic inflammation which may reduce the chance of developing

. So the role of IL-20 in

development is ambiguous and needs to be further explored. IL-20 is an angiogenesis factor and is highly expressed in artery plaques found in patients with

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually ...

In rheumatoid arthritis

IL-20 is involved in many stages of rheumatoid arthritis (RA) progression. IL-20 stimulates the secretion of

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or Cell signaling, signaling proteins secreted by Cell (biology), cells that induce directional movement of leukocytes, as well as other cell types, including endothelial a ...

MCP-1 ''For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.'' The chemokine (C-C motif) ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. C ...

and IL-8 in synovial fibroblasts, which attract

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

s and

T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...

. IL-20 is also an upstream regulator of

TNF-α Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolo ...

, IL-1, and IL-6, which are involved in the

pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...

of RA. IL-20 is highly expressed in the

synovial fluid Synovial fluid, also called synovia, elp 1/sup> is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articul ...

of RA patients. Serum levels of IL-20 are not different from those of healthy controls, suggesting that IL-20 is involved in the

of RA only at local sites of

. Receptors for IL-20 are highly expressed in the

synovial membrane The synovial membrane (also known as the synovial stratum, synovium or stratum synoviale) is a specialized connective tissue that lines the inner surface of capsules of synovial joints and tendon sheath A tendon sheath is a layer of synovial m ...

s of RA patients. Due to the clear association of IL-20 with RA, anti-IL-20 antibody is now in a clinical trial for RA.

Antibody

Anti-IL-20

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

have been researched as clinical candidates for the treatment or prevention of

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and ...

, osteoporosis, and stroke. The anti-IL-20 antibody has been shown to reduce the severity of RA in

rats Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include '' Neotoma'' ( pack rats), '' Bandicota'' (bandico ...

, mitigate bone destruction, and more. The anti-IL-20

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique m ...

neutralizes not only IL-20 signaling but also decreases

, IL-1, and IL-6 signaling in vivo. A human recombinant monoclonal antibody against IL-20 developed by Novo Nordisk Inc. now entered the IIb phase of a

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

References

External links

* {{NLM content Interleukins