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, res ...

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, cultu ...

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 are ...

. 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 interferons IL-28 and IL-29. The IL-10 family are helical cytokines categorized based on ...

. 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 autocrin ...

s, including IL-19, IL-20, IL-22, 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 intercell ...

and are almost exclusively produced by cells 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 cancer cells and objects such as wood splint ...

. IL-20 requires an IL-β-subunit receptor ( IL-20RB) for signaling, which can form a functional heterodimeric

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

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 animal coverings, such as the arthropod exoskeleton, have different de ...

, lungs, ovary,

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 testoste ...

, and

placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...

. 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 ...

s, granulocytes, and dendritic cells 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 referre ...

s and fibroblasts. 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, IL-22,

TNF 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 homolog ...

, and LPS. 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 vessel ...

, and adipocytes. 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 respons ...

) 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 again ...

, proliferation of

, prevention of apoptosis of

, regulation of differentiation of

s during

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

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

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 and society, but the term has slightly different meanings according to context. Fo ...

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 complete ...

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

Receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

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 intercell ...

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 Chronic systemic inflammation (SI) is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions ...

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 no s ...

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 signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

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. CC ...

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 ...

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 r ...

. 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 homolog ...

, 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 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 membranes 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 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 joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

, 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'' (bandicoot ...

, 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 viruses. The antibody recognizes a unique molecule of the ...

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 participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

References

External links

* {{NLM content Interleukins