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

3LTQ.pdb.png
البنية البلورية للإنترلوكن 1B البشري.[1]
Interleukin 1 / 18
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

  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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
  10. ^ 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)
  11. ^ أ ب ت ث ج ح خ د ذ ر ز س ش ص ض ط Cytokine tutorial, The University of Arizona

وصلات خارجية

قالب:Interleukin receptor modulators قالب:InterPro content