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:: جلد 23، شماره 1 - ( زمستان 1399 ) ::
جلد 23 شماره 1 صفحات 131-138 برگشت به فهرست نسخه ها
بررسی اثر اینترلوکین-۲۷ بر فعالیت سلول‌های طبیعی کشنده مغز استخوان در بیماران مبتلا به لوسمی لنفوسیتی مزمن در شرایط آزمایشگاهی
عبدالوحید صادق‌نژاد ، مارال همتی ، مهرنوش پاشایی ، زهرا رسولی نژاد ، فرحناز قهرمانفرد ، پرویز کوخایی
چکیده:   (370 مشاهده)
هدف: نقص در عملکرد سلول‌های سیستم ایمنی از مهم‌ترین علل رشد و گسترش سلول‌های توموری بوده و استفاده از سایتوکاین‌های محرک سیستم ایمنی، از جمله درمان‌های جدید در بدخیمی‌های‌خونی می‌باشد. هدف از انجام این مطالعه بررسی اثر اینترلوکین ‌27‌ (IL-27) بر‌ فعالیت سلول‌های کشنده ‌طبیعی (NK) مغز استخوان افراد مبتلا به لوسمی ‌لنفوسیتی ‌مزمن (CLL) در شرایط آزمایشگاهی بود.
مواد و روشها: ابتدا ml۱۰ آسپیره ‌مغز استخوان از ۵ بیمار مبتلا‌به CLL جمع‌آوری و سلول‌های تک‌هسته‌ای آن با استفاده از روش گرادیان فایکول جداسازی‌شده و سلول‌های NK با روش MACS تخلیص شدند. سلول‌های تک هسته‌ای (BMCs) در محیط ‌کشت RPMI در حضور‌ و عدم‌حضورIL-27 نوترکیب‌ انسانی (۱۰۰ نانوگرم در میلی‌لیتر) به مدت 48 ساعت کشت شدند. میزان بیان CD69 بر روی سلول‌های NK تخلیص‌شده و BMCs با استفاده از فلوسایتومتری مورد‌ بررسی قرار‌ گرفت. سلول‌های NK تخلیص‌شده به‌عنوان سلول‌‌ کشنده با رده‌سلولی K562 به عنوان سلول هدف در سه نسبت سلول‌ کشنده (Effector) به سلول ‌هدف (Target) (E:T) معادل با 5:1/2، 5:1 و 10:1 مجاور و میزان مرگ‌ سلول‌های هدف با استفاده از Annexin V/7-AAD بررسی‌شد.
یافتهها: مطابق نتایج به‌دست‌آمده IL-27 موجب افزایش بیان CD69 در سطح سلول‌های NK تخلیص شده، گردیده است (05/0=P)؛ در حالی‌که میزان بیان CD69 سلول‌های NK تخلیص‌ نشده (BMCs) در مجاورت با IL-27 افزایش معناداری نشان ‌نداد (06/0=P). هم‌چنین نتایج تست‌کشندگی نشان‌ داد در ‌نسبت 10:1 میزان کشندگی سلول NK افزایش معناداری داشته ‌است (3/0=P)، اما در نسبت‌های 5:1/2 و 5:1 این تفاوت معنادار‌ نمی‌باشد.
نتیجهگیری: IL-27 می‌تواند موجب تقویت عملکرد سلول‌های NK مغز استخوان در CLL شده و کشندگی آن‌ها را علیه سلول‌های ‌بدخیم افزایش دهد. حاصل دست‌آوردهای این مطالعه می‌تواند در مطالعات کارآزمایی ‌بالینی مورد استفاده قرار گیرد.
 
واژه‌های کلیدی: اینترلوکین-۲۷، لوسمی لنفوسیتی مزمن، سلول‌ کشنده طبیعی
متن کامل [PDF 1176 kb]   (53 دریافت)    
نوع مطالعه: پژوهشي | موضوع مقاله: عمومى
دریافت: 1398/10/28 | پذیرش: 1399/6/2 | انتشار: 1399/11/4
فهرست منابع
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37. [6] Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood J Am Soc Hematol 2008; 111: 5446-5456. [DOI:10.1182/blood-2007-06-093906] [PMID] [PMCID]
38. [7] Moshfeghi K, Mosayebi G. Therapeutic effects of fludarabine-cyclophosphamide combined therapy in Iranian patients with B-cell chronic lymphocytic leukemia. Koomesh 2015; 16. (Persian).
39. [8] Palma M, Kokhaei P, Lundin J, Choudhury A, Mellstedt H, Österborg A. The biology and treatment of chronic lymphocytic leukemia. Ann Oncol 2006; 17: x144-x154. [DOI:10.1093/annonc/mdl252] [PMID]
40. [9] Kumar R, Godavarthy PS, Krause DS. The bone marrow microenvironment in health and disease at a glance. J Cell Sci 2018; 131: jcs201707. [DOI:10.1242/jcs.201707] [PMID]
41. [10] Pradier A, Passweg J, Villard J, Kindler V. Human bone marrow stromal cells and skin fibroblasts inhibit natural killer cell proliferation and cytotoxic activity. Cell Transplant 2011; 20: 681-691. [DOI:10.3727/096368910X536545] [PMID]
42. [11] Moretta L, Montaldo E, Vacca P, Del Zotto G, Moretta F, Merli P, et al. Human natural killer cells: origin, receptors, function, and clinical applications. Int Arch Allergy Immunol 2014; 164: 253-264. [DOI:10.1159/000365632] [PMID]
43. [12] Nückel H, Switala M, Sellmann L, Horn P, Dürig J, Dührsen U, et al. The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia. Leukemia 2010; 24: 1152. [DOI:10.1038/leu.2010.74] [PMID]
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45. [14] Yan XJ, Dozmorov I, Li W, Yancopoulos S, Sison C, Centola M, et al. Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia. Blood 2011; 118: 5201-5210. [DOI:10.1182/blood-2011-03-342436] [PMID] [PMCID]
46. [15] Katrinakis G, Kyriakou D, Papadaki H, Kalokyri I, Markidou F, Eliopoulos GD. Defective natural killer cell activity in B-cell chronic lymphocytic leukaemia is associated with impaired release of natural killer cytotoxic factor (s) but not of tumour necrosis factor-α. Acta Haematol 1996; 96: 16-23. [DOI:10.1159/000203709] [PMID]
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49. [18] Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol 2016; 17: 1025. [DOI:10.1038/ni.3518] [PMID]
50. [19] Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One 2009; 4: e7965. [DOI:10.1371/journal.pone.0007965] [PMID] [PMCID]
51. [20] Huber M, Steinwald V, Guralnik A, Brüstle A, Kleemann P, Rosenplänter C, et al. IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol 2007; 20: 223-234. [DOI:10.1093/intimm/dxm139] [PMID]
52. [21] Matsui M, Kishida T, Nakano H, Yoshimoto K, Shin-Ya M, Shimada T, et al. Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity. Cancer Res 2009; 69: 2523-2530. [DOI:10.1158/0008-5472.CAN-08-2793] [PMID]
53. [22] Whiteside TL. Isolation of human NK cells and generation of LAK activity. Curr Protoc Immunol 1996; 17: 1-7, 11.
54. [23] Lee HR, Son CH, Koh EK, Bae JH, Kang CD, Yang K, Park YS. Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody. Sci Rep 2017; 7: 1-13. [DOI:10.1038/s41598-017-09259-1] [PMID] [PMCID]
55. [24] Shi C, Tjwa E, Biesta P, Boonstra A, Xie Q, Janssen H, Woltman A. Hepatitis B virus suppresses the functional interaction between natural killer cells and plasmacytoid dendritic cells. J Viral Hepat 2012; 19: e26-e33. [DOI:10.1111/j.1365-2893.2011.01496.x] [PMID]
56. [25] Ghojogh M, Kor Y, Rafiemanesh H. Leukemia in Iran: epidemiology and morphology trends. Asian Pac J Cancer Prev 2015; 16: 7759-7763. [DOI:10.7314/APJCP.2015.16.17.7759] [PMID]
57. [26] Forconi F, Moss P. Perturbation of the normal immune system in patients with CLL. Blood 2015; 126: 573-581. [DOI:10.1182/blood-2015-03-567388] [PMID]
58. [27] Canale S, Cocco C, Frasson C, Seganfreddo E, Di Carlo E, Ognio E, et al. Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model. Leukemia 2011; 25: 1815. [DOI:10.1038/leu.2011.158] [PMID]
59. [28] Keyser J, Schultz J, Ladell K, Elzaouk L, Heinzerling L, Pavlovic J, Moelling K. IP‐10‐encoding plasmid DNA therapy exhibits anti‐tumor and anti‐metastatic efficiency. Exp Dermatol 2004; 13: 380-390. [DOI:10.1111/j.0906-6705.2004.00191.x] [PMID]
60. [29] Dondero A, Casu B, Bellora F, Vacca A, De Luisi A, Frassanito MA, et al. NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27. Oncotarget 2017; 8: 35088. [DOI:10.18632/oncotarget.17070] [PMID] [PMCID]
61. [30] Stabile H, Nisti P, Morrone S, Pagliara D, Bertaina A, Locatelli F, et al. Multifunctional human CD56low CD16low natural killer cells are the prominent subset in bone marrow of both healthy pediatric donors and leukemic patients. Haematologica 2015; 100: 489-498. [DOI:10.3324/haematol.2014.116053] [PMID] [PMCID]
62. [31] Hemati M, Nejad ZR, Shokri MR, Ghahremanfard F, Mohammadkhani MM, Kokhaei P. IL-27 impact on NK cells activity: Implication for a robust anti-tumor response in chronic lymphocytic leukemia. Int Immunopharmacol 2020; 82: 106350. [DOI:10.1016/j.intimp.2020.106350] [PMID]
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Sadeghnejad A, Hemati M, Pashaei M, Rasouli Nejad Z, Ghahremanfard F, Kokhaei P. Effect of IL-27 on activity of bone marrow NK cells of patient with B-chronic lymphocytic leukemia in vitro. Koomesh. 2021; 23 (1) :131-138
URL: http://koomeshjournal.semums.ac.ir/article-1-6168-fa.html

صادق‌نژاد عبدالوحید، همتی مارال، پاشایی مهرنوش، رسولی نژاد زهرا، قهرمانفرد فرحناز، کوخایی پرویز. بررسی اثر اینترلوکین-۲۷ بر فعالیت سلول‌های طبیعی کشنده مغز استخوان در بیماران مبتلا به لوسمی لنفوسیتی مزمن در شرایط آزمایشگاهی. كومش. 1399; 23 (1) :131-138

URL: http://koomeshjournal.semums.ac.ir/article-1-6168-fa.html



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