Srivastava Maya D, Thomas Anil, Srivastava B I S, Check Jerome H
Division of Allergy and Immunology, The Cleveland Clinic, Cleveland, OH, USA.
Leuk Lymphoma. 2007 Aug;48(8):1610-7. doi: 10.1080/10428190701471999.
Progesterone (P), required for successful pregnancy, influences autoimmune, infectious, and malignant diseases via adaptive and innate immune effects. P induces NK inhibitor progesterone induced blocking factor (PIBF) in CD8+ T cells. PIBF isoforms could permit solid tumor immune escape. Expression and modulation of PIBF and innate immune proteins by P in leukemia cells and leukocyte subpopulations have not been reported. Ten T, seven myeloid, six B, five epithelial, fibroblast BG9, G-CSF mobilized CD34+ stem cells, and peripheral blood mononuclear cells were screened for PIBF mRNA by RT-PCR, and protein by immunohistochemistry in SRIK-NKL, MOT, U937, HL60, R-CLL, MD-E, 729pH6neo, SRIH-B(ATL), SRIK-B(T-PLL), and MeWo. Cell lines expressing PIBF and exemplifying myeloid/monoblast, natural killer/T, and B lineages were cultured with and without 0.5 - 5 microM P or 0.5 - 0.05 microM mifepristone (RU486) for 24 h. Subsequently they were examined for changes in the expression of mRNA by RT-PCR and protein by immunohistochemistry for PIBF and some innate immune factors. All cells expressed PIBF mRNA; protein only in four (SRIK-NKL, U937, SRIK-B(T-PLL) and HL60) out of 10 cell lines tested. P increased and RU486 decreased PIBF in U937, SRIK-B(T-PLL) and SRIK-NKL. P upregulated TLR-4 in U937, and HNP1 - 3, LL-37, IRAK-2, and IRAK-4 in multiple lines and RU486 down regulated these. PIBF may be used by some leukemias to evade immune surveillance and is a potential therapeutic target. P may impact infection and autoimmunity via effects on LPS receptor, TLR signaling, and antimicrobial peptides.
孕酮（P）是成功妊娠所必需的，它通过适应性免疫和固有免疫效应影响自身免疫性疾病、感染性疾病和恶性疾病。P可诱导CD8 + T细胞中的NK抑制因子——孕酮诱导阻断因子（PIBF）。PIBF亚型可能会导致实体瘤免疫逃逸。目前尚未见P对白血病细胞和白细胞亚群中PIBF及固有免疫蛋白表达和调控的报道。通过逆转录聚合酶链反应（RT-PCR）对10种T细胞系、7种髓系细胞系、6种B细胞系、5种上皮细胞系、成纤维细胞BG9、粒细胞集落刺激因子（G-CSF）动员的CD34 +干细胞以及外周血单个核细胞进行PIBF mRNA检测，并通过免疫组织化学方法对SRIK-NKL、MOT、U937、HL60、R-CLL、MD-E、729pH6neo、SRIH-B（成人T细胞白血病）、SRIK-B（T细胞幼淋巴细胞白血病）和MeWo细胞系中的PIBF蛋白进行检测。对表达PIBF且分别代表髓系/单核母细胞系、自然杀伤/T细胞系和B细胞系的细胞株，在添加或不添加0.5 - 5微摩尔/升P或0.5 - 0.05微摩尔/升米非司酮（RU486）的条件下培养24小时。随后，通过RT-PCR检测mRNA表达变化，通过免疫组织化学检测PIBF及一些固有免疫因子的蛋白表达变化。所有细胞均表达PIBF mRNA；在所检测的10种细胞系中，只有4种（SRIK-NKL、U937、SRIK-B（T细胞幼淋巴细胞白血病）和HL60）表达PIBF蛋白。P使U937、SRIK-B（T细胞幼淋巴细胞白血病）和SRIK-NKL中的PIBF增加，而RU486使其减少。P上调U937中的Toll样受体4（TLR-4），并在多种细胞系中上调人嗜中性粒细胞肽1 - 3（HNP1 - 3）、LL-37、白介素-1受体相关激酶2（IRAK-2）和白介素-1受体相关激酶4（IRAK-4），而RU486则下调这些蛋白。一些白血病可能利用PIBF逃避免疫监视，它是一个潜在的治疗靶点。P可能通过影响脂多糖受体、TLR信号传导和抗菌肽来影响感染和自身免疫。
