Share to:

 

Interleukin

Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.[1]

The function of the immune system primarily depends on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency. The majority of interleukins are synthesized by CD4 helper T-lymphocytes, as well as through monocytes, macrophages, and endothelial cells. They promote the development and differentiation of T and B lymphocytes, and hematopoietic cells.

Interleukin receptors on astrocytes in the hippocampus are also known to be involved in the development of spatial memories in mice.[2]

History and name

The name "interleukin" was chosen in 1979, to replace the various different names used by different research groups to designate interleukin 1 (lymphocyte activating factor, mitogenic protein, T-cell replacing factor III, B-cell activating factor, B-cell differentiation factor, and "Heidikine") and interleukin 2 (TSF, etc.). This decision was taken during the Second International Lymphokine Workshop in Switzerland (27–31 May 1979 in Ermatingen).[3][4][5]

The term interleukin derives from (inter-) "as a means of communication", and (-leukin) "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes". The name is something of a relic; it has since been found that interleukins are produced by a wide variety of body cells. The term was coined by Dr Vern Paetkau, University of Victoria.

Some interleukins are classified as lymphokines, lymphocyte-produced cytokines that mediate immune responses.

Common families

Interleukin 1

Main article: Interleukin 1

Interleukin 1 alpha and interleukin 1 beta (IL1 alpha and IL1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis.[6] Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors.[7] The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors.

Both IL-1 receptors (CD121a/IL1R1, CD121b/IL1R2) appear to be well conserved in evolution, and map to the same chromosomal location.[8] The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1 receptor antagonist).

The crystal structures of IL1A and IL1B[9] have been solved, showing them to share the same 12-stranded beta-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors.[10] The beta-sheets are arranged in 4 similar lobes around a central axis, 8 strands forming an anti-parallel beta-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding.

Molecular cloning of the Interleukin 1 Beta converting enzyme is generated by the proteolytic cleavage of an inactive precursor molecule. A complementary DNA encoding protease that carries out this cleavage has been cloned. Recombinant expression enables cells to process precursor Interleukin 1 Beta to the mature form of the enzyme.

Interleukin 1 also plays a role in the central nervous system. Research indicates that mice with a genetic deletion of the type I IL-1 receptor display markedly impaired hippocampal-dependent memory functioning and long-term potentiation, although memories that do not depend on the integrity of the hippocampus seem to be spared.[2][11] However, when mice with this genetic deletion have wild-type neural precursor cells injected into their hippocampus and these cells are allowed to mature into astrocytes containing the interleukin-1 receptors, the mice exhibit normal hippocampal-dependent memory function, and partial restoration of long-term potentiation.[2]

Interleukin 2

Main article: Interleukin 2

T lymphocytes regulate the growth and differentiation of T cells and certain B cells through the release of secreted protein factors.[12] These factors, which include interleukin 2 (IL2), are secreted by lectin- or antigen-stimulated T cells, and have various physiological effects. IL2 is a lymphokine that induces the proliferation of responsive T cells. In addition, it acts on some B cells, via receptor-specific binding,[13] as a growth factor and antibody production stimulant.[14] The protein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequence is required for its activity.[13] Solution NMR suggests that the structure of IL2 comprises a bundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly defined loops. Residues in helix A, and in the loop region between helices A and B, are important for receptor binding. Secondary structure analysis has suggested similarity to IL4 and granulocyte-macrophage colony stimulating factor (GMCSF).[14]

Interleukin 3

Main article: Interleukin 3

Interleukin 3 (IL3) is a cytokine that regulates hematopoiesis by controlling the production, differentiation and function of granulocytes and macrophages.[15][16] The protein, which exists in vivo as a monomer, is produced in activated T cells and mast cells,[15][16] and is activated by the cleavage of an N-terminal signal sequence.[16]

IL3 is produced by T lymphocytes and T-cell lymphomas only after stimulation with antigens, mitogens, or chemical activators such as phorbol esters. However, IL3 is constitutively expressed in the myelomonocytic leukaemia cell line WEHI-3B.[16] It is thought that the genetic change of the cell line to constitutive production of IL3 is the key event in development of this leukaemia.[16]

Interleukin 4

Main article: Interleukin 4

Interleukin 4 (IL4) is produced by CD4+ T cells specialized in providing help to B cells to proliferate and to undergo class switch recombination and somatic hypermutation. Th2 cells, through production of IL-4, have an important function in B-cell responses that involve class switch recombination to the IgG1 and IgE isotypes.

Interleukin 5

Main article: Interleukin 5

Interleukin 5 (IL5), also known as eosinophil differentiation factor (EDF), is a lineage-specific cytokine for eosinophilpoiesis.[17][18] It regulates eosinophil growth and activation,[17] and thus plays an important role in diseases associated with increased levels of eosinophils, including asthma.[18] IL5 has a similar overall fold to other cytokines (e.g., IL2, IL4 and GCSF),[18] but while these exist as monomeric structures, IL5 is a homodimer. The fold contains an anti-parallel 4-alpha-helix bundle with a left handed twist, connected by a 2-stranded anti-parallel beta-sheet.[18][19] The monomers are held together by 2 interchain disulphide bonds.[19]

Interleukin 6

Main article: Interleukin 6

Interleukin 6 (IL6), also referred to as B-cell stimulatory factor-2 (BSF-2) and interferon beta-2, is a cytokine involved in a wide variety of biological functions.[20] It plays an essential role in the final differentiation of B cells into immunoglobulin-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation, and, in hepatocytes, acute-phase reactants.[20][21]

A number of other cytokines may be grouped with IL6 on the basis of sequence similarity.[20][21][22] These include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis by affecting the production, differentiation, and function of two related white cell groups in the blood.[22] MGF also acts in hematopoiesis, stimulating proliferation and colony formation of normal and transformed avian cells of the myeloid lineage.

Cytokines of the IL6/GCSF/MGF family are glycoproteins of about 170 to 180 amino acid residues that contain four conserved cysteine residues involved in two disulphide bonds.[22] They have a compact, globular fold (similar to other interleukins), stabilised by the two disulphide bonds. One half of the structure is dominated by a 4-alpha-helix bundle with a left-handed twist;[23] the helices are anti-parallel, with two overhand connections, which fall into a double-stranded anti-parallel beta-sheet. The fourth alpha-helix is important to the biological activity of the molecule.[21]

Interleukin 7

Main article: Interleukin 7

Interleukin 7 (IL-7)[24] is a cytokine that serves as a growth factor for early lymphoid cells of both B- and T-cell lineages.

Interleukin 8

Main article: Interleukin 8

Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells[25] and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies.[26][27] In humans, the interleukin-8 protein is encoded by the CXCL8 gene.[28] IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms.[29] In culture, a 72 amino acid peptide is the major form secreted by macrophages.[29]

There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response.

Interleukin 9

Main article: Interleukin 9

Interleukin 9 (IL-9)[30] is a cytokine that supports IL-2 independent and IL-4 independent growth of helper T cells. Early studies had indicated that Interleukin 9 and 7 seem to be evolutionary related [31] and Pfam, InterPro and PROSITE entries exist for interleukin 7/interleukin 9 family. However, a recent study [32] has shown that IL-9 is, in fact, much closer to both IL-2 and IL-15, than to IL-7. Moreover, the study showed irreconcilable structural differences between IL-7 and all the remaining cytokines signalling through the γc receptor ( IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21).

Interleukin 10

Main article: Interleukin 10

Interleukin 10 (IL-10) is a protein that inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF, and GM-CSF produced by activated macrophages and by helper T cells. In structure, IL-10 is a protein of about 160 amino acids that contains four conserved cysteines involved in disulphide bonds.[33] IL-10 is highly similar to the Human herpesvirus 4 (Epstein-Barr virus) BCRF1 protein, which inhibits the synthesis of gamma-interferon and to Equid herpesvirus 2 (Equine herpesvirus 2) protein E7. It is also similar, but to a lesser degree, with human protein mda-7.[34] a protein that has antiproliferative properties in human melanoma cells. Mda-7 contains only two of the four cysteines of IL-10.

Interleukin 11

Main article: Interleukin 11

Interleukin 11 (IL-11) is a secreted protein that stimulates megakaryocytopoiesis, initially thought to lead to an increased production of platelets (it has since been shown to be redundant to normal platelet formation), as well as activating osteoclasts, inhibiting epithelial cell proliferation and apoptosis, and inhibiting macrophage mediator production. These functions may be particularly important in mediating the hematopoietic, osseous and mucosal protective effects of interleukin 11.[35]

Interleukin 12

Main article: Interleukin 12

Interleukin 12 (IL-12) is a disulphide-bonded heterodimer consisting of a 35kDa alpha subunit and a 40kDa beta subunit. It is involved in the stimulation and maintenance of Th1 cellular immune responses, including the normal host defence against various intracellular pathogens, such as Leishmania, Toxoplasma, Measles virus, and Human immunodeficiency virus 1 (HIV). IL-12 also has an important role in enhancing the cytotoxic function of NK cells[36][37] and role in pathological Th1 responses, such as in inflammatory bowel disease and multiple sclerosis. Suppression of IL-12 activity in such diseases may have therapeutic benefit. On the other hand, administration of recombinant IL-12 may have therapeutic benefit in conditions associated with pathological Th2 responses.[38][39]

Interleukin 13

Main article: Interleukin 13

Interleukin 13 (IL-13) is a pleiotropic cytokine that may be important in the regulation of the inflammatory and immune responses.[40] It inhibits inflammatory cytokine production and synergises with IL-2 in regulating interferon-gamma synthesis. The sequences of IL-4 and IL-13 are distantly related.[41]

Interleukin 15

Main article: Interleukin 15

Interleukin 15 (IL-15) is a cytokine that possesses a variety of biological functions, including stimulation and maintenance of cellular immune responses.[42] IL-15 stimulates the proliferation of T lymphocytes, which requires interaction of IL-15 with IL-15R alpha and components of IL-2R, including IL-2R beta and IL-2R gamma (common gamma chain, γc), but not IL-2R alpha.

Interleukin 17

Main article: Interleukin 17

Interleukin 17 (IL-17) is a potent proinflammatory cytokine produced by activated memory T cells.[43] This cytokine is characterized by its proinflammatory properties, role in recruiting neutrophils, and importance in innate and adaptive immunity. Not only does IL-17 play a key role in inflammation of many autoimmune diseases, such as RA, allergies, asthma, psoriasis, and more, but it also plays a key role in the pathogenesis of these diseases. Additionally, some studies have found that IL-17 plays a role in tumorigenesis (initial formation of a tumor) and transplant rejection.[44] The IL-17 family is thought to represent a distinct signaling system that appears to have been highly conserved across vertebrate evolution.[43]

In humans

Name Source[45] Targets Function[45]
Receptors[45][46] Cells[45]
IL-1 macrophages, B cells, monocytes,[47] dendritic cells [47] CD121a/IL1R1, CD121b/IL1R2 T helper cells co-stimulation [47]
B cells maturation and proliferation [47]
NK cells activation[47]
macrophages, endothelium, other inflammation,[47] small amounts induce acute phase reaction, large amounts induce fever
IL-2 Th1-cells CD25/IL2RA, CD122/IL2RB, CD132/IL2RG activated[47] T cells and B cells, NK cells, macrophages, oligodendrocytes stimulates growth and differentiation of T cell response. Can be used in immunotherapy to treat cancer or suppressed for transplant patients. Has also been used in clinical trials (ESPIRIT. Stalwart) to raise CD4 counts in HIV positive patients.
IL-3 activated T helper cells,[47] mast cells, NK cells, endothelium, eosinophils CD123/IL3RA, CD131/IL3RB hematopoietic stem cells differentiation and proliferation of myeloid progenitor cells [47] to e.g. erythrocytes, granulocytes
mast cells growth and histamine release[47]
IL-4 Th2 cells, just activated naive CD4+ cell, memory CD4+ cells, mast cells, macrophages CD124/IL4R, CD132/IL2RG activated B cells proliferation and differentiation, IgG1 and IgE synthesis.[47] Important role in allergic response (IgE)
T cells proliferation[47]
endothelium increase expression of vascular cell adhesion molecule (VCAM-1) promoting adhesion of lymphocytes.[48]
IL-5 Th2 cells, mast cells, eosinophils CD125/IL5RA, CD131/IL3RB eosinophils production
B cells differentiation, IgA production
IL-6 macrophages, Th2 cells, B cells, astrocytes, endothelium CD126/IL6RA, CD130/IL6RB activated B cells differentiation into plasma cells
plasma cells antibody secretion
hematopoietic stem cells differentiation
T cells, others induces acute phase reaction, hematopoiesis, differentiation, inflammation
IL-7 Bone marrow stromal cells and thymus stromal cells CD127/IL7RA, CD132/IL2RG pre/pro-B cell, pre/pro-T cell, NK cells differentiation and proliferation of lymphoid progenitor cells, involved in B, T, and NK cell survival, development, and homeostasis, ↑proinflammatory cytokines
IL-8 or CXCL8 macrophages, lymphocytes, epithelial cells, endothelial cells CXCR1/IL8RA, CXCR2/IL8RB/CD128 neutrophils, basophils, lymphocytes Neutrophil chemotaxis
IL-9 Th2 cells, specifically by CD4+ helper cells CD129/IL9R T cells, B cells Potentiates IgM, IgG, IgE, stimulates mast cells
IL-10 monocytes, Th2 cells, CD8+ T cells, mast cells, macrophages, B cell subset CD210/IL10RA, CDW210B/IL10RB macrophages cytokine production[47]
B cells activation [47]
mast cells
Th1 cells inhibits Th1 cytokine production (IFN-γ, TNF-β, IL-2)
Th2 cells Stimulation
IL-11 bone marrow stroma IL11RA bone marrow stroma acute phase protein production, osteoclast formation
IL-12 dendritic cells, B cells, T cells, macrophages CD212/IL12RB1, IR12RB2 activated [47] T cells, differentiation into Cytotoxic T cells with IL-2,[47] ↑ IFN-γ, TNF-α, ↓ IL-10
NK cells ↑ IFN-γ, TNF-α
IL-13 activated Th2 cells, mast cells, NK cells IL13R Th2 cells, B cells, macrophages Stimulates growth and differentiation of B cells (IgE), inhibits Th1 cells and the production of macrophage inflammatory cytokines (e.g. IL-1, IL-6), ↓ IL-8, IL-10, IL-12
IL-14 T cells and certain malignant B cells activated B cells controls the growth and proliferation of B cells, inhibits Ig secretion
IL-15 mononuclear phagocytes (and some other cells), especially macrophages following infection by virus(es) IL15RA T cells, activated B cells Induces production of Natural killer cells
IL-16 lymphocytes, epithelial cells, eosinophils, CD8+ T cells CD4 CD4+ T cells (Th-cells) CD4+ chemoattractant
IL-17 T helper 17 cells (Th17) CDw217/IL17RA, IL17RB epithelium, endothelium, other osteoclastogenesis, angiogenesis, ↑ pro-inflammatory cytokines
IL-18 macrophages CDw218a/IL18R1 Th1 cells, NK cells Induces production of IFN-γ, ↑ NK cell activity
IL-19 - IL20R -
IL-20 Activated keratinocytes and monocytes IL20R regulates proliferation and differentiation of keratinocytes
IL-21 activated T helper cells, NKT cells IL21R All lymphocytes, dendritic cells costimulates activation and proliferation of CD8+ T cells, augment NK cytotoxicity, augments CD40-driven B cell proliferation, differentiation and isotype switching, promotes differentiation of Th17 cells
IL-22 T helper 17 cells (Th17) IL22R Production of defensins from epithelial cells.[36] Activates STAT1 and STAT3 and increases production of acute phase proteins such as serum amyloid A, Alpha 1-antichymotrypsin and haptoglobin in hepatoma cell lines
IL-23 macrophages, dendritic cells IL23R Maintenance of IL-17 producing cells,[36] increases angiogenesis but reduces CD8 T-cell infiltration
IL-24 melanocytes, keratinocytes, monocytes, T cells IL20R Plays important roles in tumor suppression, wound healing and psoriasis by influencing cell survival, inflammatory cytokine expression.
IL-25 T Cells, mast cells, eosinophils, macrophages, mucosal epithelial cells LY6E Induces the production IL-4, IL-5 and IL-13, which stimulate eosinophil expansion
IL-26 T cells, monocytes IL20R1 Enhances secretion of IL-10 and IL-8 and cell surface expression of CD54 on epithelial cells
IL-27 macrophages, dendritic cells IL27RA Regulates the activity of B lymphocyte and T lymphocytes
IL-28 - IL28R Plays a role in immune defense against viruses
IL-29 - Plays a role in host defenses against microbes
IL-30 - Forms one chain of IL-27
IL-31 Th2 cells IL31RA May play a role in inflammation of the skin
IL-32 - Induces monocytes and macrophages to secrete TNF-α, IL-8 and CXCL2
IL-33 epithelial cells Induces helper T cells to produce type 2 cytokine
IL-35 regulatory T cells Suppression of T helper cell activation
IL-36 - Regulates DC and T cell responses

International nonproprietary names for analogues and derivatives

Endogenous form name Pharmaceutical form INN suffix INNs
interleukin-1 (IL-1) -nakin
interleukin-1α (IL-1α) -onakin pifonakin
interleukin-1β (IL-1β) -benakin mobenakin
interleukin-2 (IL-2) -leukin adargileukin alfa, aldesleukin, celmoleukin, denileukin diftitox, pegaldesleukin, teceleukin, tucotuzumab celmoleukin
interleukin-3 (IL-3) -plestim daniplestim, muplestim
interleukin-4 (IL-4) -trakin binetrakin
interleukin-6 (IL-6) -exakin atexakin alfa
interleukin-8 (IL-8) -octakin emoctakin
interleukin-10 (IL-10) -decakin ilodecakin
interleukin-11 (IL-11) -elvekin oprelvekin
interleukin-12 (IL-12) -dodekin edodekin alfa
interleukin-13 (IL-13) -tredekin cintredekin besudotox
interleukin-18 (IL-18) -octadekin iboctadekin

References

  1. ^ Brocker C, Thompson D, Matsumoto A, Nebert DW, Vasiliou V (Oct 2010). "Evolutionary divergence and functions of the human interleukin (IL) gene family". Human Genomics. 5 (1): 30–55. doi:10.1186/1479-7364-5-1-30. PMC 3390169. PMID 21106488.
  2. ^ a b c Ben Menachem-Zidon O, Avital A, Ben-Menahem Y, Goshen I, Kreisel T, Shmueli EM, Segal M, Ben Hur T, Yirmiya R (Jul 2011). "Astrocytes support hippocampal-dependent memory and long-term potentiation via interleukin-1 signaling". Brain, Behavior, and Immunity. 25 (5): 1008–16. doi:10.1016/j.bbi.2010.11.007. PMID 21093580. S2CID 18300021.
  3. ^ di Giovine FS, Duff GW (Jan 1990). "Interleukin 1: the first interleukin". Immunology Today. 11 (1): 13–20. doi:10.1016/0167-5699(90)90005-t. PMID 2405873.
  4. ^ Schindler R, Dinarello CA (1990). "Interleukin 1". In Habenicht A (ed.). Growth Factors, Differentiation Factors, and Cytokines. Berlin, Heidelberg: Springer. pp. 85–102. doi:10.1007/978-3-642-74856-1_7. ISBN 978-3-642-74856-1.
  5. ^ "Revised nomenclature for antigen-nonspecific T cell proliferation and helper factors". Journal of Immunology. 123 (6): 2928–9. Dec 1979. doi:10.4049/jimmunol.123.6.2928. PMID 91646.
  6. ^ Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, Grubin CE, Wignall JM, Jackson JL, Call SM (Jul 1988). "cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily". Science. 241 (4865): 585–9. Bibcode:1988Sci...241..585S. doi:10.1126/science.2969618. PMID 2969618.
  7. ^ Liu C, Hart RP, Liu XJ, Clevenger W, Maki RA, De Souza EB (Aug 1996). "Cloning and characterization of an alternatively processed human type II interleukin-1 receptor mRNA". The Journal of Biological Chemistry. 271 (34): 20965–72. doi:10.1074/jbc.271.34.20965. PMID 8702856.
  8. ^ McMahan CJ, Slack JL, Mosley B, Cosman D, Lupton SD, Brunton LL, Grubin CE, Wignall JM, Jenkins NA, Brannan CI (Oct 1991). "A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types". The EMBO Journal. 10 (10): 2821–32. doi:10.1002/j.1460-2075.1991.tb07831.x. PMC 452992. PMID 1833184.
  9. ^ Priestle JP, Schär HP, Grütter MG (Dec 1989). "Crystallographic refinement of interleukin 1 beta at 2.0 A resolution". Proceedings of the National Academy of Sciences of the United States of America. 86 (24): 9667–71. doi:10.1073/pnas.86.24.9667. PMC 298562. PMID 2602367.
  10. ^ Murzin AG, Lesk AM, Chothia C (Jan 1992). "beta-Trefoil fold. Patterns of structure and sequence in the Kunitz inhibitors interleukins-1 beta and 1 alpha and fibroblast growth factors". Journal of Molecular Biology. 223 (2): 531–43. doi:10.1016/0022-2836(92)90668-A. PMID 1738162.
  11. ^ Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G, Yirmiya R (2003). "Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity". Hippocampus. 13 (7): 826–34. CiteSeerX 10.1.1.513.8947. doi:10.1002/hipo.10135. PMID 14620878. S2CID 8368473.
  12. ^ Yokota T, Arai N, Lee F, Rennick D, Mosmann T, Arai K (Jan 1985). "Use of a cDNA expression vector for isolation of mouse interleukin 2 cDNA clones: expression of T-cell growth-factor activity after transfection of monkey cells". Proceedings of the National Academy of Sciences of the United States of America. 82 (1): 68–72. Bibcode:1985PNAS...82...68Y. doi:10.1073/pnas.82.1.68. PMC 396972. PMID 3918306.
  13. ^ a b Cerretti DP, McKereghan K, Larsen A, Cantrell MA, Anderson D, Gillis S, Cosman D, Baker PE (May 1986). "Cloning, sequence, and expression of bovine interleukin 2". Proceedings of the National Academy of Sciences of the United States of America. 83 (10): 3223–7. Bibcode:1986PNAS...83.3223C. doi:10.1073/pnas.83.10.3223. PMC 323485. PMID 3517854.
  14. ^ a b Mott HR, Driscoll PC, Boyd J, Cooke RM, Weir MP, Campbell ID (Aug 1992). "Secondary structure of human interleukin 2 from 3D heteronuclear NMR experiments". Biochemistry. 31 (33): 7741–4. doi:10.1021/bi00148a040. PMID 1510960.
  15. ^ a b Dorssers L, Burger H, Bot F, Delwel R, Geurts van Kessel AH, Löwenberg B, Wagemaker G (1987). "Characterization of a human multilineage-colony-stimulating factor cDNA clone identified by a conserved noncoding sequence in mouse interleukin-3". Gene. 55 (1): 115–24. doi:10.1016/0378-1119(87)90254-X. PMID 3497843.
  16. ^ a b c d e Ymer S, Tucker WQ, Sanderson CJ, Hapel AJ, Campbell HD, Young IG (1985). "Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene". Nature. 317 (6034): 255–8. Bibcode:1985Natur.317..255Y. doi:10.1038/317255a0. PMID 2413359. S2CID 4279226.
  17. ^ a b Campbell HD, Tucker WQ, Hort Y, Martinson ME, Mayo G, Clutterbuck EJ, Sanderson CJ, Young IG (Oct 1987). "Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5)". Proceedings of the National Academy of Sciences of the United States of America. 84 (19): 6629–33. Bibcode:1987PNAS...84.6629C. doi:10.1073/pnas.84.19.6629. PMC 299136. PMID 3498940.
  18. ^ a b c d Milburn MV, Hassell AM, Lambert MH, Jordan SR, Proudfoot AE, Graber P, Wells TN (May 1993). "A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5". Nature. 363 (6425): 172–6. Bibcode:1993Natur.363..172M. doi:10.1038/363172a0. PMID 8483502. S2CID 4254991.
  19. ^ a b Proudfoot AE, Davies JG, Turcatti G, Wingfield PT (May 1991). "Human interleukin-5 expressed in Escherichia coli: assignment of the disulfide bridges of the purified unglycosylated protein". FEBS Letters. 283 (1): 61–4. Bibcode:1991FEBSL.283...61P. doi:10.1016/0014-5793(91)80553-F. PMID 2037074. S2CID 39101523.
  20. ^ a b c Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A (1986). "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin". Nature. 324 (6092): 73–6. Bibcode:1986Natur.324...73H. doi:10.1038/324073a0. PMID 3491322. S2CID 4367596.
  21. ^ a b c Lütticken C, Krüttgen A, Möller C, Heinrich PC, Rose-John S (May 1991). "Evidence for the importance of a positive charge and an alpha-helical structure of the C-terminus for biological activity of human IL-6". FEBS Letters. 282 (2): 265–7. Bibcode:1991FEBSL.282..265L. doi:10.1016/0014-5793(91)80491-K. PMID 2037043. S2CID 42023451.
  22. ^ a b c Clogston CL, Boone TC, Crandall BC, Mendiaz EA, Lu HS (Jul 1989). "Disulfide structures of human interleukin-6 are similar to those of human granulocyte colony stimulating factor". Archives of Biochemistry and Biophysics. 272 (1): 144–51. doi:10.1016/0003-9861(89)90205-1. PMID 2472117.
  23. ^ Walter MR, Cook WJ, Zhao BG, Cameron RP, Ealick SE, Walter RL, Reichert P, Nagabhushan TL, Trotta PP, Bugg CE (Oct 1992). "Crystal structure of recombinant human interleukin-4". The Journal of Biological Chemistry. 267 (28): 20371–6. doi:10.2210/pdb2int/pdb. PMID 1400355. S2CID 2310949.
  24. ^ Henney CS (May 1989). "Interleukin 7: effects on early events in lymphopoiesis". Immunology Today. 10 (5): 170–3. doi:10.1016/0167-5699(89)90175-8. PMID 2663018.
  25. ^ Hedges JC, Singer CA, Gerthoffer WT (2000). "Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes". Am. J. Respir. Cell Mol. Biol. 23 (1): 86–94. CiteSeerX 10.1.1.326.6212. doi:10.1165/ajrcmb.23.1.4014. PMID 10873157.
  26. ^ Wolff B, Burns AR, Middleton J, Rot A (1998). "Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies". J. Exp. Med. 188 (9): 1757–62. doi:10.1084/jem.188.9.1757. PMC 2212526. PMID 9802987.
  27. ^ Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G (1998). "Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells". J. Exp. Med. 188 (9): 1751–6. doi:10.1084/jem.188.9.1751. PMC 2212514. PMID 9802986.
  28. ^ Modi WS, Dean M, Seuanez HN, Mukaida N, Matsushima K, O'Brien SJ (1990). "Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily". Hum. Genet. 84 (2): 185–7. doi:10.1007/BF00208938. PMID 1967588. S2CID 2217894.
  29. ^ a b Brat DJ, Bellail AC, Van Meir EG (2005). "The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis". Neuro-Oncology. 7 (2): 122–133. doi:10.1215/s1152851704001061. PMC 1871893. PMID 15831231.
  30. ^ Renauld JC, Goethals A, Houssiau F, Merz H, Van Roost E, Van Snick J (Jun 1990). "Human P40/IL-9. Expression in activated CD4+ T cells, genomic organization, and comparison with the mouse gene". Journal of Immunology. 144 (11): 4235–41. doi:10.4049/jimmunol.144.11.4235. PMID 1971295. S2CID 30151082.
  31. ^ Boulay JL, Paul WE (September 1993). "Hematopoietin sub-family classification based on size, gene organization and sequence homology". Current Biology. 3 (9): 573–81. Bibcode:1993CBio....3..573B. doi:10.1016/0960-9822(93)90002-6. PMID 15335670. S2CID 42479456.
  32. ^ Reche PA (February 2019). "The tertiary structure of γc cytokines dictates receptor sharing". Cytokine. 116: 161–168. doi:10.1016/j.cyto.2019.01.007. PMID 30716660. S2CID 73449371.
  33. ^ Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A (Jun 1995). "Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma". Structure. 3 (6): 591–601. doi:10.1016/S0969-2126(01)00193-9. PMID 8590020.
  34. ^ Jiang H, Lin JJ, Su ZZ, Goldstein NI, Fisher PB (Dec 1995). "Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression". Oncogene. 11 (12): 2477–86. PMID 8545104.
  35. ^ Leng SX, Elias JA (1997). "Interleukin-11". The International Journal of Biochemistry & Cell Biology. 29 (8–9): 1059–62. doi:10.1016/S1357-2725(97)00017-4. PMID 9416001.
  36. ^ a b c Abbas AK, Lichtman AH, Pillai S (2012). Cellular and molecular immunology (7th ed.). Philadelphia: Elsevier/Saunders. ISBN 978-1437715286.
  37. ^ Zhang C, Zhang J, Niu J, Zhou Z, Zhang J, Tian Z (Aug 2008). "Interleukin-12 improves cytotoxicity of natural killer cells via upregulated expression of NKG2D". Human Immunology. 69 (8): 490–500. doi:10.1016/j.humimm.2008.06.004. PMID 18619507.
  38. ^ Park AY, Scott P (Jun 2001). "Il-12: keeping cell-mediated immunity alive". Scandinavian Journal of Immunology. 53 (6): 529–32. doi:10.1046/j.1365-3083.2001.00917.x. PMID 11422900. S2CID 32020154.
  39. ^ Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, Presky DH (1998). "The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses". Annual Review of Immunology. 16: 495–521. doi:10.1146/annurev.immunol.16.1.495. PMID 9597139.
  40. ^ Minty A, Chalon P, Derocq JM, Dumont X, Guillemot JC, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B (Mar 1993). "Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses". Nature. 362 (6417): 248–50. Bibcode:1993Natur.362..248M. doi:10.1038/362248a0. PMID 8096327. S2CID 4368915.
  41. ^ Seyfizadeh N, Seyfizadeh N, Gharibi T, Babaloo Z (December 2015). "Interleukin-13 as an important cytokine: A review on its roles in some human diseases" (PDF). Acta Microbiologica et Immunologica Hungarica. 62 (4): 341–78. doi:10.1556/030.62.2015.4.2. PMID 26689873.
  42. ^ Arena A, Merendino RA, Bonina L, Iannello D, Stassi G, Mastroeni P (Apr 2000). "Role of IL-15 on monocytic resistance to human herpesvirus 6 infection". The New Microbiologica. 23 (2): 105–12. PMID 10872679.
  43. ^ a b Aggarwal S, Gurney AL (January 2002). "IL-17: prototype member of an emerging cytokine family". Journal of Leukocyte Biology. 71 (1): 1–8. doi:10.1189/jlb.71.1.1. PMID 11781375. S2CID 15271840.
  44. ^ Tesmer LA, Lundy SK, Sarkar S, Fox DA (June 2008). "Th17 cells in human disease". Immunological Reviews. 223: 87–113. doi:10.1111/j.1600-065X.2008.00628.x. PMC 3299089. PMID 18613831.
  45. ^ a b c d Unless else specified in boxes, then ref is: Lippincott's Illustrated Reviews: Immunology. Paperback: 384 pages. Publisher: Lippincott Williams & Wilkins; (July 1, 2007). Language: English. ISBN 0-7817-9543-5. ISBN 978-0-7817-9543-2. Page 68
  46. ^ Alaverdi N, Sehy D (2007-05-01). "Cytokines - Master Regulators of the Immune System" (PDF). eBioscience. Archived from the original (PDF) on 2006-03-15. Retrieved 2008-02-28.
  47. ^ a b c d e f g h i j k l m n o p Cytokine tutorial, The University of Arizona Archived 2008-02-02 at the Wayback Machine
  48. ^ Kotowicz K, Callard RE, Friedrich K, Matthews DJ, Klein N (Dec 1996). "Biological activity of IL-4 and IL-13 on human endothelial cells: functional evidence that both cytokines act through the same receptor". Int Immunol. 8 (12): 1915–25. doi:10.1093/intimm/8.12.1915. PMID 8982776.
This article incorporates text from the public domain Pfam and InterPro: IPR000779
Kembali kehalaman sebelumnya