Cytokines are a category of signalling proteins and glycoproteins that, like hormones and neurotransmitters, are used extensively in cellular communication. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body See Chemical synapse for an introduction to concepts and terminology used in this article Cell signaling is part of a Complex system of Communication that governs basic cellular activities and coordinates cell actions While hormones are secreted from specific organs to the blood, and neurotransmitters are related to neural acitivity, the cytokines are a more diverse class of compounds in terms of origin and purpose. They are produced by a wide variety of hematopoietic and non-hematopoietic cell types and can have effects on both nearby cells or throughout the organism, sometimes strongly dependent on the presence of other chemicals. Haematopoiesis (from Ancient Greek haima blood poiesis to make (or hematopoiesis in the United States sometimes also haemopoiesis or The cytokine family consists mainly of smaller, water-soluble proteins and glycoproteins with a mass of between 8 and 30 kDa. The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express
Cytokines are critical to the functioning of both innate and adaptive immune responses. They are often secreted by immune cells which have encountered a pathogen as a way to activate and recruit more immune cells and increase the system's response to the pathogen. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious However, apart from their role in the development and functioning of the immune system, as well as their aberrant modes of secretion in a variety of immunological, inflammatory and infectious diseases, cytokines are also involved in several developmental processes during embryogenesis. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Embryogenesis is the process by which the Embryo is formed and develops
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Effects
Each cytokine binds to a specific cell-surface receptor. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling Subsequent cascades of intracellular signaling then alter cell functions. A biochemical cascade is a series of Chemical reactions in which the products of one reaction are consumed in the next reaction This may include the upregulation and/or downregulation of several genes and their transcription factors, in turn resulting in the production of other cytokines, an increase in the number of surface receptors for other molecules, or the suppression of their own effect by feedback inhibition. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity.
The effect of a particular cytokine on a given cell depends on the cytokine, its extracellular abundance, the presence and abundance of the complementary receptor on the cell surface, and downstream signals activated by receptor binding; these last two factors can vary by cell type. Cytokines are characterized by considerable "redundancy", in that many cytokines appear to share similar functions.
Generalization of functions is not possible with cytokines; nonetheless, their actions may be grouped as:
- autocrine, if the cytokine acts on the cell that secretes it
- paracrine, if the action is restricted to the immediate vicinity of a cytokine's secretion
- endocrine, if the cytokine diffuses to distant regions of the body (carried by blood or plasma) to affect different tissues. Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent that binds to autocrine receptors on the same cell leading Paracrine signaling is a form of Cell signaling in which the target cell is near (" Para " = near the signal-releasing cell The endocrine system is an integrated system of small organs that involve the release of extracellular signaling molecules known as Hormones The endocrine system is instrumental
It seems to be a paradox that cytokines binding to antibodies have a stronger immune effect than the cytokine alone. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily This may lead to lower therapeutic doses and perhaps fewer side-effects.
Overstimulation of cytokines can trigger a dangerous syndrome known as a cytokine storm; this may have been the cause of severe adverse events during a clinical trial of TGN1412. A cytokine storm is a potentially fatal immune reaction consisting of a Positive feedback loop between Cytokines and Immune cells with highly elevated TGN1412 (also known as CD28-SuperMAB) is the working name of an Immunomodulatory drug which was withdrawn from development originally intended for the treatment of
Nomenclature
Cytokines have been variously named as lymphokines, interleukins, and chemokines, based on their presumed function, cell of secretion, or target of action. Lymphokines are a subset of Cytokines that are produced by a type of Immune cell known as a Lymphocyte. Interleukins are a group of Cytokines (secreted Signaling molecules) that were first seen to be expressed by White blood cells ( Leukocytes hence Chemokines are a family of small Cytokines, or Proteins secreted by cells Proteins are classified as chemokines according to shared structural characteristics Because cytokines are characterized by considerable redundancy and pleiotropism, such distinctions, allowing for exceptions, are obsolete.
- The term interleukin was initially used by researchers for those cytokines whose presumed targets are principally leukocytes. It is now used largely for designation of newer cytokine molecules discovered every day and bears little relation to their presumed function. The vast majority of these are produced by T-helper cells. T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or
- The term chemokine refers to a specific class of cytokines that mediates chemoattraction (chemotaxis) between cells. Chemotaxis, a kind of Taxis, is the phenomenon in which bodily cells bacteria, and other single-cell or Multicellular organisms direct their movements
IL-8 (interleukin-8) is the only chemokine originally named an interleukin. Interleukin-8 (IL-8 is a Chemokine produced by Macrophages and other cell types such as epithelial cells
Classification
Structural
Structural homology has been able to partially distinguish between cytokines that do not demonstrate a considerable degree of redundancy so that they can be classified into four types:
- The four α-helix bundle family - Member cytokines have three-dimensional structures with four bundles of α-helices. A common motif in the Secondary structure of Proteins the alpha helix (α-helix is a right-handed coiled conformation resembling a spring, in which This family in turn is divided into three sub-families:
- the IL-2 subfamily
- the interferon (IFN) subfamily
- the IL-10 subfamily. Interleukin-2 ( IL-2) is an Interleukin, a type of Cytokine Immune system signaling molecule that is instrumental in the body's natural response Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents Interleukin -10 (IL-10 or IL10 also known as human cytokine synthesis inhibitory factor (CSIF is an anti- Inflammatory Cytokine.
- the IL-1 family, which primarily includes IL-1 and IL-18
- the IL-17 family, which has yet to be completely characterized, though member cytokines have a specific effect in promoting proliferation of T-cells that cause cytotoxic effects
- Chemokines. Interleukin-1 (IL-1 is one of the first Cytokines ever described Interleukins are a group of Cytokines (secreted Signaling molecules) that were first seen to be expressed by White blood cells ( Leukocytes hence Interleukins are a group of Cytokines (secreted Signaling molecules) that were first seen to be expressed by White blood cells ( Leukocytes hence Chemokines are a family of small Cytokines, or Proteins secreted by cells Proteins are classified as chemokines according to shared structural characteristics
Functional
A classification that proves more useful in clinical and experimental practice divides immunological cytokines into those that enhance cytokine responses, type 1 ( IFN-γ, TGF-β etc. ), and type 2 (IL-4, IL-10, IL-13, etc. Interleukin-4, abbreviated IL-4, is a Cytokine that induces differentiation of naive helper T cells ( Th0 cells to Th2 cells Upon activation by Interleukin -10 (IL-10 or IL10 also known as human cytokine synthesis inhibitory factor (CSIF is an anti- Inflammatory Cytokine. Interleukin 13 ( IL-13) is a Cytokine secreted by many cell types but especially T helper type 2 (Th2 cells that is an important mediator of allergic ), which favor antibody responses.
A key focus of interest has been that cytokines in one of these two sub-sets tend to inhibit the effects of those in the other. Dysregulation of this tendency is under intensive study for its possible role in the pathogenesis of autoimmune disorders. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues
Cytokine receptors
In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been directly linked to certain debilitating immunodeficiency states. A Cytokine receptor is a receptor which binds Cytokines In recent years the cytokine receptors have come to demand the attention of more investigators than cytokines In this regard, and also because the redundancy and pleiomorphism of cytokines are, in fact, a consequence of their homologous receptors, many authorities are now of the opinion that a classification of cytokine receptors would be more clinically and experimentally useful.
A classification of cytokine receptors based on their three-dimensional structure has, therefore, been attempted. Such a classification, though seemingly cumbersome, provides several unique perspectives for attractive pharmacotherapeutic targets.
- Immunoglobulin (Ig) superfamily, which are ubiquitously present throughout several cells and tissues of the vertebrate body, and share structural homology with immunoglobulins (antibodies), cell adhesion molecules, and even some cytokines. The immunoglobulin superfamily (IgSF is a large group of cell surface and soluble proteins that are involved in the recognition binding or adhesion processes of cells In Evolutionary biology, homology has come to mean any similarity between characters that is due to their shared ancestry. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Cell Adhesion Molecules ( CAM s are Proteins located on the cell surface involved with the Binding with other cells or with the Extracellular Examples: IL-1 receptor types.
- Haemopoietic Growth Factor (type 1) family, whose members have certain conserved motifs in their extracellular amino-acid domain. The term growth factor refers to a naturally occurring Protein capable of stimulating cellular growth proliferation and Cellular differentiation. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this The IL-2 receptor belongs to this chain, whose γ-chain (common to several other cytokines) deficiency is directly responsible for the x-linked form of Severe Combined Immunodeficiency (X-SCID). Severe combined immunodeficiency ( SCID) or Boy in the Bubble Syndrome is a genetic disorder in which both "arms" ( B cells and T cells X-linked Severe Combined Immunodeficiency (X-SCID is a profound and severe Immunodeficiency characterized by the complete absence of NK cells and T cells
- Interferon (type 2) family, whose members are receptors for IFN β and γ. Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents
- Tumor necrosis factors (TNF) (type 3) family, whose members share a cysteine-rich common extracellular binding domain, and includes several other non-cytokine ligands like CD40, CD27 and CD30, besides the ligands on which the family is named (TNF). Tumor necrosis factors (or the TNF-family) refers to a group of Cytokines family that can cause Apoptosis. Not to be confused with Cystine, its oxidized dimer Cysteine (abbreviated as Cys or C) is an α- Amino acid with In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally CD40 is a costimulatory protein found on Antigen presenting cells and is required for their activation CD27 is a Tumor necrosis factor receptor. CD30, also known as TNFRSF8, is a cell membrane
- Seven transmembrane helix family, the ubiquitous receptor type of the animal kingdom. G protein-coupled receptors ( GPCRs) also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, and All G-protein coupled receptors (for hormones and neurotransmitters) belong to this family. G protein-coupled receptors ( GPCRs) also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, and Chemokine receptors, two of which act as binding proteins for HIV (CXCR4 and CCR5), also belong to this family. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome CXCR4, (a '''CXC''' chemokine '''R'''eceptor) also called fusin, is an alpha- Chemokine receptor specific for stromal-derived-factor-1 ( SDF-1 CCR5, short for chemokine (C-C motif receptor 5, is a Chemokine receptor.
Cysteine-knot cytokines
Members of the transforming growth factor beta superfamily belong to this group, including TGF-β1, TGF-β2 and TGF-β3. The transforming growth factor beta (TGF-β superfamily is a large family of structurally related cell regulatory Proteins that was named after its first member TGF-β1 Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the Transforming growth factor beta superfamily of Cytokines It is a secreted protein Transforming growth factor-beta 2 (TGF-β2 is a secreted protein known as a Cytokine that performs many cellular functions and has a vital role during Embryonic development Transforming growth factor-beta 3 (TGF-β3 is a type of protein known as a Cytokine, which is involved in Cell differentiation, Embryogenesis and
References
- Gallin J, Snyderman R (eds). Inflammation: Basic Principles and Clinical Correlates. 3rd edition, Philadelphia, Lippincott William and Wilkins, 1999.
- Janeway CA et al. (eds). Immunobiology. The immune system in Health and Disease, 4th edition, New York, Garland, 1999.
- Roitt I et al. (eds. ) Immunology. 5th edition, London, Mosby, 2002.
- Science Vol. Science is the Academic journal of the American Association for the Advancement of Science and is considered one of the world's most prestigious Scientific 311 No. 5769, pp. 1875 - 1876, 31 March 2006 DOI: 10.1126/science.1126030
See also
- Adipokines
- Apoptosis
- Chemokines
- Cytokine secretion assay
- Cytokine storm
- ELISA assays
- ELISPOT assays
- Interleukins
- Interferon
- Granulocyte-colony stimulating factor
- Signal transduction
- Tumor necrosis factors
External links
- Cytokine Tutorial
- Cell Interactions: Cytokines
- Reperfusion Injury in Stroke. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. The adipokines or adipocytokines are a group of Cytokines ( cell -to-cell signalling Proteins secreted by Adipose tissue. Chemokines are a family of small Cytokines, or Proteins secreted by cells Proteins are classified as chemokines according to shared structural characteristics Secretion assay is a process used in Cell biology to identify cells that are secreting a particular Protein (usually a Cytokine) A cytokine storm is a potentially fatal immune reaction consisting of a Positive feedback loop between Cytokines and Immune cells with highly elevated Enzyme-Linked ImmunoSorbent Assay, also called ELISA, Enzyme ImmunoAssay or EIA, is a biochemical technique used mainly in Immunology The Enzyme-linked immunosorbent spot ( ELISPOT) assay is a common method for monitoring immune responses in humans and animals Interleukins are a group of Cytokines (secreted Signaling molecules) that were first seen to be expressed by White blood cells ( Leukocytes hence Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents Granulocyte colony-stimulating factor ( G-CSF or GCSF) is a Colony-stimulating factor hormone In Biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another Tumor necrosis factors (or the TNF-family) refers to a group of Cytokines family that can cause Apoptosis.
- Cytokines Online Pathfinder Encyclopaedia
- Cytokines and inflammation, science and practical journal
Dictionary
cytokine
-noun
- (biochemistry, immunology) Any of various small regulatory proteins that regulate the cells of the immune system.
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