Adenylate cyclase (AC): An enzyme of the lyase class that catalyzes the formation of cyclic AMP (cyclic 3',5'‑monophosphate AMP [cAMP]) from adenosine triphosphate.

Adenosine cyclic 3',5'‑monophosphate (cAMP): A cyclic nucleotide that serves as an important second messenger in intracellular signal transduction.

Adenosine monophosphate (AMP), or adenylic acid: A condensation product of adenosine and phosphoric acid; a nucleotide found among the hydrolysis products of all nucleic acids. 3'‑Adenylic acid (adenosine 3'‑monophosphate) and 5'‑adenylic acid [adenosine 5'‑monophosphate (AMP)] differ in the place of attachment of the phosphoric acid to the D‑ribose; deoxyadenylic acid differs in having H instead of OH at the 2' position of D‑ribose.

Ankylosing spondylitis (AS): arthritis of the spine, resembling rheumatoid arthritis, which may progress to bony ankylosis with ossification of the anterior and posterior longitudinal ligaments; the disease is more common in males, often with the rheumatoid factor absent and the HLA antigen present. A striking association with the B27 tissue type and the strong familial aggregation suggests an important genetic factor, perhaps inherited as an autosomal dominant [MIM*106300]; the mechanism, however, remains obscure.

Antigen: Any substance that, as a result of coming in contact with appropriate cells, induces a state of sensitivity or immune responsiveness and that reacts in a demonstrable way with antibodies or immune cells of the sensitized subject in vivo or in vitro.

Anti‑inflammatory: Reducing inflammation by acting on body responses without directly antagonizing the causative agent.

Autoimmune: Pertaining to cells and antibodies that arise from and are directed against the individual's own tissues.

B cells (or B lymphocyte): One of the 2 major types of lymphocytes. B cells express but do not release surface immunoglobulins. B cells are the precursors of plasma cells, which are active in the formation and secretion of antibodies.

Cell: The smallest unit of living structure capable of independent existence, composed of a membrane‑enclosed mass of protoplasm containing a nucleus or nucleoid.

Cell membrane: The protoplasmic boundary of all cells, which controls permeability and may serve other functions.

Chemical knockout: Genetic knockout involves the genetic engineering of an organism in which the genome has been altered by site‑directed recombination so that a gene is deleted. In chemical knockout, saturation doses of selective inhibitors are used to prevent expression or activity of a gene product.

Chemokine (C‑C motif) ligand 2 (CCL2): A cytokine that is structurally related to the CXC subfamily of cytokines, which are characterized by two cysteines separated by a single amino acid. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, such as psoriasis. It binds to chemokine receptors CCR2 and CCR4.

Chemokine (C‑C motif) ligand 3 (CCL3): A small inducible cytokine, also known as macrophage inflammatory protein 1 alpha, that plays a role in inflammatory responses through binding to the receptors CCR1, CCR4, and CCR5.

Chemokines: Small proteins that stimulate the migration and activation of cells, especially phagocytic cells and lymphocytes.

Chemotaxis: Movement of cells or organisms toward (positive chemotaxis) or away from (negative chemotaxis) substances exhibiting certain chemical properties.

Chondrocyte: A cartilage cell that occupies a lacuna within the cartilage matrix.

Class Ia phosphatidylinositol 3‑kinase (PI3K): A phosphatidylinositol 3‑kinase subclass that includes enzymes formed through the heterodimerization of a p110 catalytic and a p85, p55, or p50 regulatory subunit. This subclass of enzymes is a downstream target of tyrosine kinase receptors and G‑protein‑coupled receptors.

Cyclic adenosine monophosphate (cAMP): An activator of phosphorylase kinase and an effector of other enzymes, formed in muscle from ATP by adenylate cyclase and broken down to 5'‑AMP by a phosphodiesterase; the first known second messenger, it is a regulator of metabolism. A related compound (2',3') is also known.

Cyclic AMP Response Element-Binding Protein (CREB): A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated calcium-calmodulin-dependent protein kinases. This protein functions to integrate both calcium and cAMP signals.

Cyclic guanosine monophosphate (cGMP): an analogue of cAMP; a second messenger for atrial natriuretic factor.

Cyclic nucleotide phosphodiesterase, type 4 (PDE4): A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of cell‑mediated immunity.

Cytokine: Any of numerous hormonelike, low‑molecular‑weight proteins, secreted by various cell types, which regulate the intensity and duration of immune response and mediate cell‑to‑cell communication.

Cytoplasm: The substance of the protoplasm of a cell, exclusive of the nucleus.

Dactylitis: Inflammation of one or more fingers.

Dendritic cells: Bone marrow‑derived cells found throughout the lymphatic system and in skin and epithelia; dendritic cells trap and process antigens and present them to T cells, thereby stimulating cell‑mediated immunity.

Differentiation: The acquisition or possession of one or more characteristics or functions different from that of the original type.

Effector: Something that causes an effect; an effector cell is a lymphocyte (eg, a T cell) that has been induced to differentiate into a form (eg, a cytotoxic T cell) capable of mounting an immune response.

Endothelial cells: Flat cells that line blood vessels, lymphatic vessels, and the heart.

Enthesitis: Inflammation at the site of muscle insertion.

Eukaryote: A member of the superkingdom Eukaryotae, consisting of organisms made up of cells that contain a membrane‑bound nucleus that contains chromosomes; the Eukaryotae includes some single‑celled organisms as well as all fungi, plants, and animals.

Extracellular‑signal‑related kinase (ERK): Also called classical MAP kinase, the ERKs are widely expressed intracellular enzymes that are involved in regulating many processes related to meiosis, mitosis, and postmitotic functions in differentiated cells.

Fibroblast: A stellate or spindle‑shaped cell with cytoplasmic processes present in connective tissue, capable of forming collagen fibers.

Guanine nucleotide binding protein (G protein), alpha subunit (GαS): One of the 3 nonidentical subunits of the guanosine nucleotide‑binding proteins (G proteins) that serve as molecular switches attached to G‑protein‑coupled receptors.

IκB kinase (IKK): A protein serine threonine kinase that catalyzes the phosphorylation of iκB proteins. This enzyme also activates the transcription factor NF‑κB and is composed of α and β catalytic subunits, which are protein kinases and gamma, a regulatory subunit.

Immune response: Any response made by an organism to an antigen.

Immune system: A coordinated system of cells, tissues, and soluble products that constitutes the body's defense against invasion by nonself entities, including infectious and inert agents and tumor cells.

Immunoglobulins: Multisubunit proteins that function in immunity; they include antibodies and B‑cell receptors.

Inflammation (or inflammatory response): The general term for histologically apparent cytologic changes, cellular infiltration, and mediator release that occurs in affected blood vessels and adjacent tissue in response to injury or abnormal stimulation. The so‑called cardinal signs of rubor (redness), calor (heat), tumor (swelling), and dolor (pain) may or may not be present.

Inflammatory: Pertaining to, characterized by, causing, resulting from, or becoming affected by inflammation.

Innate immunity: resistance by an individual that has not been immunized or sensitized by prior exposure; innate immunity is nonspecific and not stimulated by specific antigens.

Interferons (IFN): Cytokines produced by T cells, fibroblasts, and other cells in response to viral infection and other biologic and synthetic stimuli; IFNs bind to specific receptors on cell membranes.

Interleukin (IL): Any of a group of multifunctional cytokines synthesized by lymphocytes, monocytes, macrophages, and lymphoid and nonlymphoid cells.

Interleukin‑6 (IL‑6): A cytokine derived from macrophages and endothelial cells that increases synthesis and secretion of immunoglobulins by B lymphocytes; also induces acute‑phase proteins; also called interferon β2.

Interleukin‑10 (IL‑10): A cytokine derived from helper T cell lymphocytes (Th2) that inhibits mononuclear cell inflammation.

Intracellular: Within a cell or cells.

Janus kinase (JAK): A family of nonspecific protein‑tyrosine kinases activated by binding of cytokines to their plasma membrane receptors; the kinases, bound to the cytoplasmic domains of the receptors, serve as intermediates linking the receptors to activation of the STAT family of transcription factors, which migrate to the nucleus to regulate gene expression.

c‑Jun‑N‑terminal kinase (JNK): A subgroup of mitogen‑activated protein kinases that activate transcription factor AP‑1 via the phosphorylation of c‑Jun proteins. They are components of intracellular signaling pathways that regulate cell proliferation, apoptosis, and cell differentiation.

Keratinocyte: A cell of the living epidermis and certain oral epithelium that produces keratin in the process of differentiating into the dead and fully keratinized cells of the stratum corneum.

Leukotriene: Products of eicosanoid metabolism (usually, arachidonate) with several physiologic roles, such as mediation of inflammation and participation in allergic reactions; leukotrienes differ from the related prostaglandins and thromboxanes in that they do not have a central ring; so named because they were discovered in association with leukocytes and were initially determined to possess three conjugated double bonds; letters A‑F identify the first six metabolites isolated, with subscript numbers to indicate the number of double bonds (eg, leukotriene C4).

Lymphoid cells: White blood cells of the immune system.

Macrophages: Large mononuclear phagocytic cells important as scavenger cells, as pathogen recognition cells and sources of proinflammatory cytokines in innate immunity, as antigen‑presenting cells, and as effector phagocytic cells in humoral and cell‑mediated immunity.

Macrophage inflammatory protein (MIP): a member of the chemokine family that is chemotactic for certain lymphocyte subsets such as T‑cytotoxic cells.

Mitogen‑associated protein kinase (MAPK): Any of several cytoplasmic protein kinases that make up the MAPK signaling cascade.

Mitogen‑associated protein kinase p38 (MPAK p38): A mitogen‑activated protein kinase subfamily that regulates a variety of cellular processes, including cell growth processes, cell differentiation, apoptosis, and cellular responses to inflammation. The p38 map kinases are regulated by cytokine receptors and can be activated in response to bacterial pathogens.

Monocytes: White blood cells with a bean‑shaped nucleus. Monocytes that leave the bloodstream and enter the connective tissue spaces are called macrophages.

Monocyte chemoattractant protein‑1 (MCP‑1): secreted by endothelial cells of a blood vessel wall; it induces extravasation of monocytes.

Nuclear factor of κ light polypeptide gene enhancer in B cells (NF‑κB): NF‑κB is a transcription regulator that is activated by various intra‑ and extra‑cellular stimuli such as cytokines, oxidant‑free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NF‑κB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions.

Neutrophils: The major class of white blood cell in human peripheral blood. Neutrophils are phagocytes with an important role in entering infected tissues and engulfing and killing extracellular pathogens.

Pathogenesis: The origin or cause of the pathology of a disease.

Pathogen: Any microorganism that can cause disease when it infects a host.

Phagocyte: A cell that can ingest bacteria, foreign particles, and other cells.

Phosphodiesterase (PDE): Enzymes that cleave bonds in phosphodiesters, such as those in cAMP.

Phosphatidylinositol 3‑kinase (PI3K): A phosphatidylinositol 3‑kinase subclass that includes enzymes formed through the heterodimerization of a p110 catalytic and a p85, p55, or p50 regulatory subunit. This subclass of enzymes is a downstream target of tyrosine kinase receptors and G‑protein‑coupled receptors.

Phosphodiesterase 4 (PDE4): A key enzyme involved in the cytokine production of inflammatory cells. PDE4 is an intracellular enzyme that promotes inflammation by degrading intracellular levels of cyclic adenosine monophosphate (cAMP), a naturally occurring second messenger that helps maintain immune homeostasis by modulating the production of pro‑ and anti‑inflammatory mediators.

Proinflammatory cytokines: Cytokines that promote inflammation. They are structurally related but may contain rather diverse functions (TNF/TNF receptor superfamily and IL‑1 superfamily).

Psoriasis: A common dermatologic condition characterized by the eruption of circumscribed, discrete and confluent, reddish, silvery‑scaled maculopapules; the lesions occur predominantly on the elbows, knees, scalp, and trunk, and microscopically show characteristic parakeratosis and elongation of rete ridges with shortening of epidermal keratinocyte transit time due to decreased cyclic guanosine monophosphate

Protein kinase A (PKA): A group of enzymes that are dependent on cyclic AMP and catalyze the phosphorylation of serine or threonine residues on proteins. Included under this category are two cyclic‑AMP‑dependent protein kinase subtypes, each of which is defined by its subunit composition.

Protein kinase C (PKC): A serine‑threonine protein kinase that requires the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor‑promoting phorbol esters.

Psoriatic Arthritis: A form of polyarthritis (ie, affecting more than one joint) that occurs in patients with psoriasis; the arthritis resembles rheumatoid arthritis but is seronegative for rheumatoid factor and often involves the digits.

Receptor: A structural protein molecule on the cell surface or within the cytoplasm that binds to a specific factor, such as a drug, hormone, antigen, or neurotransmitter.

Signal transducer and activator of transcription (STAT): A family of transcription factors containing SH2 domains that are involved in cytokine‑mediated signal transduction. STAT transcription factors are recruited to the cytoplasmic region of cell surface receptors and are activated via phosphorylation. Once activated, they dimerize and translocate into the cell nucleus, where they influence gene expression. They play a role in regulating cell growth processes and cell differentiation. STAT transcription factors are inhibited by suppressors of cytokine signaling proteins and protein inhibitors of activated STAT.

Spleen tyrosine kinase (Syk): A non‑receptor tyrosine kinase critical for signaling B‑cell activation.

Spondyloarthropathy: Any of several diseases (as ankylosing spondylitis) affecting the joints of the spine. See ankylosing spondylitis (AS).

Synovium: Synovial membrane; the layer of cells that line the joint cavity; the site of production of synovial fluid that provides the nutrition of the articular cartilage and lubricates the cartilage surfaces.

T cell receptor (TCR): A disulfide‑linked heterodimer of the highly variable α and β chains or γ and δ chains expressed on the cell membrane of T lymphocytes as a complex with the invariant CD3 chains.

T lymphocytes: Also called T cells; a subset of lymphocytes that are formed in bone marrow and migrate to the thymus, where they become immunocompetent; T cells are responsible for cell‑mediated immunity; T lymphocytes have characteristic T cell receptor‑CD3 complexes as surface markers and may be further categorized by function, such as helper and cytotoxic.

Transcription: Transfer of genetic code information from one kind of nucleic acid to another, especially with reference to the process by which a base sequence of messenger RNA is synthesized on a template of complementary DNA.

Transcription factors: Endogenous substances, usually proteins, that are effective in the initiation, stimulation, or termination of the genetic transcription process.

Tumor necrosis factor (TNF): Any of several cytokines that function as cell‑associated or secreted proteins interacting with receptors of the tumor necrosis factor receptor (TNFR) family.

Thymus‑ and activation‑regulated chemokine (TARC)/CCL17: A lymphocyte‑directed CC chemokine that plays a role in the recruitment of CC chemokine receptor‑4‑positive T helper 2 (Th2) cells.

Tumor necrosis factor alpha (TNF‑α): Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF‑α, it is only 30% homologous to TNF‑β (lymphotoxin), but they share TNF receptors.

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See PDE4’s Role in Autoimmune Disease

See PDE4's Role in Autoimmune Disease
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