إنترلوكن
إنترلوكن Interleukin هي مجموعة من السايتوكينات (پروتينات/جزيئات اشارة مـُـفرَزة) شوهدت لأول مرة في خلايا الدم البيضاء. يحفز جهاز المناعة في الجسم ليقاوم الاحتقان والمرض. وتتشكل الإنترلوكينات في مجموعة واسعة من خلايا الجسم، منها خلايا الدم البيضاء التي تُسَمَّى أيضًا الكُريَّات البيضاء. وهذه الخلايا تطرد أو تدمر البكتيريا والمواد الأخرى الضارة التي تدخل الجسم.
تُوجد أنواع مختلفة من الإنترلوكينات في الأنماط المختلفة لخلايا الدم البيضاء. وهنالك ثلاثة أنواع من الإنترلوكينات قد أُشبعت درسًا، هي: إنترلوكين 1، وإنترلوكين 2، و إنترلوكين 3. وتعمل هذه الإنترلوكينات معًا وتُحدث سلسلة من ردود الأفعال التي من شأنها أن تسلِّح خلايا الدم البيضاء في الجسم ضد المرض. فمثلاً، إذا أُصِبْت بجرح، ودخلت البكتيريا الجرح تقوم خلايا الدَّم البيضاء بالكشف عن وجود البكتيريا في موقع الجرح. وبعدها تتولى هذه الخلايا إطلاق إنترلوكين 1، وهو بدوره يعطي الإشارة لخلايا دم بيضاء أُخرى، ُتدْعى الخلايا التائية لتساعد في تدمير البكتيريا. وبدورها تقوم الخلايا التائية بإطلاق إنترلوكين ـ2 والكيميائيات المشابهة، التي تحفز مختلف الخلايا في نظام المناعة لتشن الهجوم. انظر: المناعة. وهناك دلائل مبشرة على جدوى معالجة الإنترلوكينات للسرطان وأمراض أُخرى كثيرة. ويمكن إنتاج كل من إنترلوكين 1، 2 في المختبر.
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العائلات الشائعة للإنترلوكنات
إنترلوكن 1
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| البنية البلورية للإنترلوكن 1B البشري.[1] | |
Interleukin 1 / 18
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| المميزات | |
| الرمز | IL1 |
| Pfam | PF00340 |
| InterPro | IPR000975 |
| SMART | SM00125 |
| SCOP | 1i1b |
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.[2] 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.[3] 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.[4] 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[5] 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.[6] 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.[7][8] 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.[7]
قائمة الإنترلوكنات البشرية
| الاسم | المصدر [9] | المستقبلات المستهدفة[9][10] | الخلايا المستهدفة[9] | الوظيفة[9] |
| إل-1 | macrophages, B cells, monocytes [11], dendritic cells [11] | CD121a/IL1R1, CD121b/IL1R2 | T helper cells | co-stimulation [11] |
| B cells | maturation & proliferation [11] | |||
| الخلايا القاتلة | activation[11] | |||
| macrophages, endothelium, other | التهاب[11], small amounts induce acute phase reaction, large amounts induce fever | |||
| إل-2 | TH1-cells | CD25/IL2RA, CD122/IL2RB, CD132/IL2RG | activated[11] T cells and B cells, الخلايا القاتلة, macrophages, oligodendrocytes | stimulates growth and differentiation of T cell response. Can be used in immunotherapy to treat cancer or suppressed for transplant patients. |
| إل-3 | activated T helper cells[11], mast cells, الخلايا القاتلة, endothelium, eosinophils | CD123/IL3RA, CD131/IL3RB | hematopoietic stem cells | differentiation and proliferation of myeloid progenitor cells [11] to e.g. erythrocytes, granulocytes |
| mast cells | growth and histamine release[11] | |||
| إل-4 | TH2 cells, just activated naive CD4+ cell, [[memory CD4+ cells]s, mast cells, macrophages | CD124/IL4R, CD132/IL2RG | activated B cells | proliferation and differentiation, IgG1 and IgE synthesis[11]. Important role in allergic response (IgE) |
| T cells | proliferation[11] | |||
| endothelium | ||||
| إل-5 | TH2 cells, mast cells, eosinophils | CD125/IL5RA, CD131/IL3RB | eosinophils | production |
| B cells | differentiation, IgA production | |||
| إل-6 | macrophages, TH2-cells, B cells, astrocytes, endothelium | CD126/IL6RA, CD130/IR6RB | activated B cells | differentiation into plasma cells |
| plasma cells | افراز الأجسام المضادة | |||
| hematopoietic stem cells | differentiation | |||
| T cells, others | induces acute phase reaction, hematopoiesis, differentiation, inflammation | |||
| إل-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 |
| إل-8 | macrophages, lymphocytes, epithelial cells, endothelial cells | CXCR1/IL8RA, CXCR2/IL8RB/CD128 | neutrophils, basophils, lymphocytes | Neutrophil chemotaxis |
| إل-9 | Th2 cells, specifically by CD4+ helper cells | CD129/IL9R | T cells, B cells | Potentiates IgM, IgG, IgE, stimulates mast cells |
| إل-10 | monocytes, TH2 cells, CD8+ T cells, mast cells, macrophages, B cell subset | CD210/IL10RA, CDW210B/IL10RB | macrophages | cytokine production[11] |
| B cells | activation [11] | |||
| mast cells | ||||
| Th1 cells | inhibits Th1 cytokine production (IFN-γ, TNF-β, إل-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 [11] T cells, | differentiation into Cytotoxic T cells with IL-2[11], ↑ IFN-γ, TNF-α, ↓ IL-10 |
| الخلايا القاتلة | ↑ 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, ↑ inflammatory cytokines |
| IL-18 | macrophages | CDw218a/IL18R1 | Th1 cells, NK cells | Induces production of IFNγ, ↑ NK cell activity |
| IL-19 | - | IL20R | - | |
| IL-20 | - | 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 | - | IL22R | 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 | - | IL23R | Increases angiogenesis but reduces CD8 T-cell infiltration | |
| IL-24 | - | IL20R | Plays important roles in tumor suppression, wound healing and psoriasis by influencing cell survival. | |
| IL-25 | - | LY6E | Induces the production IL-4, IL-5 and IL-13, which stimulate eosinophil expansion | |
| IL-26 | - | IL20R1 | Enhances secretion of IL-10 and IL-8 and cell surface expression of CD54 on epithelial cells | |
| IL-27 | - | IL27RA | Regulates the activity of B lymphocyte and T lymphocytes | |
| IL-28 | - | IL28R | Plays a role in immune defense against viruses | |
| إل-29 | - | Plays a role in host defenses against microbes | ||
| IL-30 | - | Forms one chain of IL-27 | ||
| IL-31 | - | 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 | - | Induces helper T cells to produce type 2 cytokine | ||
| IL-35 | regulatory T cells | Suppression of T helper cell activation | ||
| IL-36 | - | ينظم DC and T cell responses |
INNs (أسماء دولية غير مسجلة الملكية) للمضاهيات والمشتقات الصيدلانية
| 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 |
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الهامش
- ^ PDB 3LTQ; Barthelmes K, Reynolds AM, Peisach E, Jonker HR, DeNunzio NJ, Allen KN, Imperiali B, Schwalbe H (Feb 2011). "Engineering encodable lanthanide-binding tags into loop regions of proteins". Journal of the American Chemical Society. 133 (4): 808–19. doi:10.1021/ja104983t. PMC 3043167. PMID 21182275.
- ^ 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. doi:10.1126/science.2969618. PMID 2969618.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ أ ب 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.
- ^ 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.
- ^ أ ب ت ث 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 0781795435. ISBN 978-0781795432. Page 68
- ^ Noosheen Alaverdi & David Sehy (2007-05-01). "Cytokines - Master Regulators of the Immune System" (PDF). eBioscience. Retrieved 2008-02-28.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help) - ^ أ ب ت ث ج ح خ د ذ ر ز س ش ص ض ط Cytokine tutorial, The University of Arizona