Interleukin 17A
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Interleukin 17A
Interleukin-17A is a protein that in humans is encoded by the ''IL17A'' gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene (). Function The protein encoded by this gene is a proinflammatory cytokine produced by activated T cells. This cytokine regulates the activities of NF-kappaB and mitogen-activated protein kinases. This cytokine can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). Discovery IL-17A, often referred to as IL-17, was originally discovered at transcriptional level by Rouvier et al. in 1993 from a rodent T-cell hybridoma, derived from the fusion of a mouse cytotoxic T cell clone and a rat T cell lymphoma. Human and mouse IL-17A were cloned a few years later by Yao and Kennedy. Lymphocytes including CD4+, CD8+, gamma-delta T (γδ-T), invariant NKT and innate lymphoid cells (ILCs) are primary sources of IL-17A. Non-T cells, such as neutro ...
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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, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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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 involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months. While the cause of rheumatoid arthritis is not clear, it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves the body's immune system attacking the joints. This results in inflammation and thickening of the joint capsule. It also affects the underlying bone and cartilage. The diagnosis is made mos ...
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Ulcerative Colitis
Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and anemia may also occur. Often, symptoms come on slowly and can range from mild to severe. Symptoms typically occur intermittently with periods of no symptoms between flares. Complications may include abnormal dilation of the colon (megacolon), inflammation of the eye, joints, or liver, and colon cancer. The cause of UC is unknown. Theories involve immune system dysfunction, genetics, changes in the normal gut bacteria, and environmental factors. Rates tend to be higher in the developed world with some proposing this to be the result of less exposure to intestinal infections, or to a Western diet and lifestyle. The removal of the appendix at an early age may be protective. Diagnosis is typically by colonoscopy with tissue biopsies. It is ...
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Crohn's Disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension, and weight loss. Complications outside of the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and fatigue. The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum. Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer. While the precise causes of Crohn's disease (CD) are unknown, it is believed to be caused by a combination of environmental, immune, and bacterial factors in genetically susceptible individuals. It results in a chronic inflammatory disorder, in which the body's immune system defends the gastrointestinal tract, possibly targeting microbial ...
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Ixekizumab
Ixekizumab, sold under the brand name Taltz, is an injectable medication for the treatment of autoimmune diseases. Chemically, it is a form of a humanized monoclonal antibody. The substance acts by binding interleukin 17A and neutralizing it, reducing inflammation. The most common side effects include upper respiratory infections, injection site reactions and fungal (tinea) infections. The drug was developed by Eli Lilly and Company, Eli Lilly and Co. and is approved for the treatment of plaque psoriasis in the European Union and the United States. Medical uses In the United States, ixekizumab is Indication (medicine), indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy, active psoriatic arthritis, active ankylosing spondylitis, and active non-radiographic axial spondyloarthritis with objective signs of inflammation. In the European Union it is indicated for the treatment of moderate-to-severe ...
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Secukinumab
Secukinumab, sold under the brand name Cosentyx, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis. Medical uses Secukinumab is used to treat psoriasis, ankylosing spondylitis, and psoriatic arthritis. It is given by subcutaneous injection and is sold in a pre-filled syringe or autoinjector that can be used at home and as a lyophilized powder for use in hospitals and clinics. Secukinumab was not tested in pregnant women; animal studies did not show harm at relevant doses. The US Food and Drug Administration advises that the drug should be used in pregnant women only if the risk to the fetus is justified by the potential benefit; the European Medicines Agency (EMA) advises that women should not become pregnant while taking it. Secukinumab should not be given to people with active infections since it suppresses the immune system. ...
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Interleukin 12
Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B- lymphoblastoid cells ( NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects. Gene and structure IL12 is a heterodimeric cytokine encoded by two separate genes, IL-12A (p35) and IL-12B (p40). The active heterodimer (referred to as 'p70'), and a homodimer of p40 are formed following protein synthesis. IL12A is composed of a bundle of four alpha helices. IL12B has three beta sheet domains. Functions IL-12 is involved in the differentiation of naive T cells into Th1 cells. It is known as a T cell-stimulating factor, which can stimulate the growth and function of T cells. It stimulate ...
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Tumor Necrosis Factor Alpha
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 homologous TNF domain. As an adipokine, TNF promotes insulin resistance, and is associated with obesity-induced type 2 diabetes. As a cytokine, TNF is used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF signaling occurs through two receptors: TNFR1 and TNFR2. TNFR1 is constituitively expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells. TNFR1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation. Suppression of TNFR1 signaling has been important for ...
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Interferon Gamma
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the ''IFNG'' gene. Through cell signaling, IFN-γ plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by type II IFN is the JAK-STAT signal ...
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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 body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon. The five main types of psoriasis are plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. It typically presents as red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp. Guttate psoriasis has drop-shaped lesions. Pustular psoriasis presents as small, noninfectious, pus-filled blisters. Inverse psoriasis forms red patches in skin folds. Erythrodermic psoriasis occurs when the rash becomes very widespread, and can develop from any of the other types. ...
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Blood–brain Barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where neurons reside. The blood–brain barrier is formed by endothelial cells of the Capillary, capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive transport, passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function. The blood–brain barrier restricts the passage of pathogens, the diffusion of solutes in the blood, and Molecular mass, large or Hydrophile, hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of Hydr ...
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Experimental Autoimmune Encephalomyelitis
Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE), is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general. EAE was motivated by observations during the convalescence from viral diseases by Thomas M. Rivers, D. H. Sprunt and G. P. Berry in 1933. Their findings upon a transfer of inflamed patient tissue to primates was published in the ''Journal of Experimental Medicine''. An acute monophasic illness, it has been suggested that EAE is far more similar to ADEM than MS. Types of EAE EAE can be induced in a number of species, including mice, rats, guinea pigs, rabbits and primates. The most commonly u ...
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