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| The effect of TNF on hematopoietic regulation and its role in high altitude polycythemia |
| Xie Youbang1 Nian Wei2 Liu Yanmin3 Gao Yunmei1 Shi Xuefeng4 Xi Aiqi5 |
1.Department of Hematology and Rheumatology, Qinghai Provincial People’s Hospital, Qinghai Province, Xi’ning 810007, China;
2.Department of Geriatrics, Qinghai Provincial People’s Hospital, Qinghai Province, Xi’ning 810007, China;
3.Department of Cardiovascular Intervention, Qinghai Provincial People’s Hospital, Qinghai Province, Xi’ning 810007, China;
4.Department of Respiratory and Intensive Care Unit, Qinghai Provincial People’s Hospital, Qinghai Province, Xi’ning 810007, China;
5.Department of Geriatrics, the Fourth People’s Hospital of Qinghai Province, Qinghai Province, Xi’ning 810000, China |
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Abstract As one of the hematopoietic inhibitors, there are two main types of tumor necrosis factor (TNF) family: TNF-α and TNF-β. The effects of the two on stem cells and progenitor cells are different under different colony stimulating factor (CSF) stimulation. TNF-α activates nuclear factor-κB (NF-κB) through its classical pathway, in which inhibitor-κ binding protein (IκB) is phosphorylated and releases NF-κB dimer, which translocates to the nucleus to bind specific NF-κB DNA. The binding site activates gene expression and positively regulates gene transcription involved in the maintenance and homeostasis of hematopoietic stem cells (HSC) and progenitor cells. TNF-α activates Notch and NF-κB signal transduction pathways through TNFR2, and promotes HSC production under inflammatory signal transduction. TNF-β receptor also named lymphotoxin-β receptor (LTβR) which expresses in many hematopoietic tissues. TNF-β can activate the NF-κB signaling pathway to produce a series of biological effects. LTβR signaling leads to NF-κB activation in a cell type-restricted manner. The level of TNF-β in bone marrow supernatant of high altitude polycythemia (HAPC) was significantly increased. There is PI3K/Akt signaling pathway activation in bone marrow CD71+ cells of HAPC. The above suggests that TNF-β may play an important role in the erythropoiesis regulation of HAPC.
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[1] Villafuerte FC，Corante N. Chronic mountain mickness：clinical aspects，etiology，management，and treatment [J]. High Alt Med Biol，2016，17（2）：61-69.
[2] Wu TY，Li W，Li Y，et al. Epidemiology of chronic mountain sickness：ten years’ study in Qinghai-Tibet [C]//Progress in Mountain Medicine and High Altitude Physiology. Matsumoto，Japan：Press Committee of the Third World Congress on Mountain Medicine and High Altitude Physiology，1998，120：125.
[3] Sahota IS，Panwar NS. Prevalence of chronic mountain sickness in high altitude districts of Himachal Pradesh [J]. Indian J Occup Environ Med，2013，17（3）：94.
[4] Brenner R，Pratali L，Rimoldi SF，et al. Exaggerated pulmonary hypertension and right ventricular dysfunction in high-altitude dwellers with patent foramen ovale [J]. Chest，2015，147（4）：1072-1079.
[5] Guan W，Ga Q，Li R，et al. Sleep disturbances in long-term immigrants with chronic mountain sickness：A comparison with healthy immigrants at high altitude [J]. Respir Physiol Neurobiol，2015，206：4-10.
[6] 冯建明，孙志新，王建国.高原红细胞增多症骨髓病理及超微结构研究[J].中华内科杂志，1998，37（12）：3-5.
[7] 叶冬梅，李占全，冀林华，等.Monge病患者血清P53和Bcl-xL蛋白表达水平及意义[J].青海医学院学报，2007， 28（3）：158-161.
[8] 孙敏敏，崔森，李占全，等.慢性高原病患者骨髓有核红细胞凋亡及Bcl-2表达研究[J].中华临床医师杂志：电子版，2013，7（10）：4281-4284.
[9] Leon-Velarde F，Mejía O. Gene expression in chronic high altitude diseases [J]. High Alt Med Biol，2008，9（2）：130-139.
[10] 郭新建.高原红细胞增多症骨髓缺氧诱导因子的表达分析[J].高原医学杂志，2007，17（2）：20-21.
[11] Gonzales GF，Gasco M，Tapia V，et al. High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men [J]. Am J Physiol Endocrinol Metab，2009，296（6）：E1319-E1325.
[12] 李素芝，薛增军，牟信兵，等.高原红细胞增多症患者血清血小板生成素水平的检测[J].中华血液学杂志，1999， 20（11）：3-5.
[13] 刘舒，裴澍萱，张世馥，等.高原红细胞增多症患者与高原健康人血浆EPO，IL-3，IL-6含量及相关性分析[J].中华医学杂志，2001，22（3）：45.
[14] 李建平，贾乃镛，李占全，等.高原红细胞增多症患者骨髓单个核细胞GATA-1和GATA-2表达研究[J].中华血液学杂志，2007，28（8）：537-540.
[15] 苏娟，贾乃镛，李占全，等.高原红细胞增多症患者骨髓单个核细胞磷酸化STAT5和p38-MAPK水平研究[J].中华血液学杂志，2008，29（12）：836-837.
[16] Appenzeller O，Minko T，Qualls C，et al. Chronic hypoxia in Andeans：are there lessons for neurology at sea level? [J]. J Neurol Sci，2006，247（1）：93-99.
[17] Degliantoni G，Murphy M，Kobayashi M，et al. Natural killer（NK）cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon [J]. J Exp Med，1985，162（5）：1512-1530.
[18] Lamikanra AA，Merryweather-Clarke AT，Tipping AJ，et al. Distinct mechanisms of inadequate erythropoiesis induced by tumor necrosis factor alpha or malarial pigment [J]. PLoS One，2015，10（3）：e0119836.
[19] Mizrahi K，Askenasy N. Physiological functions of TNF family receptor/ligand interactions in hematopoiesis and transplantation [J]. Blood，2014，124（2）：176-183.
[20] Brown KD，Claudio E，Siebenlist U. The roles of the classical and alternative nuclear factor-kappaB pathways：potential implications for autoimmunity and rheumatoid arthritis [J]. Arthritis Res Ther，2008，10（4）：212.
[21] Stein SJ，Baldwin AS. Deletion of the NF-kappaB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function [J]. Blood，2013，121（25）：5015-5024.
[22] Espin-Palazon R，Stachura DL，Campbell CA，et al. Proinflammatory signaling regulates hematopoietic stem cell emergence [J]. Cell，2014，159（5）：1070-1085.
[23] Tian T，Wang M，Ma D. TNF-alpha，a good or bad factor in hematological diseases? [J]. Stem Cell Investig，2014，1：12.
[24] Basak S，Hoffmann A. Crosstalk via the NF-κB signaling system [J]. Cytokine Growth Factor Rev，2008，19（3/4）：187-197.
[25] Kaushansky K，Broudy VC，Harlan JM，et al. Tumor necrosis factor-alpha and tumor necrosis factor-beta（lymphotoxin）stimulate the production of granulocyte-macrophage colony-stimulating factor，macrophage colony-stimulating factor，and IL-1 in vivo [J]. J immunol，1988，141（10）：3410-3415.
[26] Sizemore N，Leung S，Stark GR. Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to phosphorylation and activation of the NF-kappaB p65/RelA subunit [J]. Mol Cell Biol，1999，19（7）：4798-4805.
[27] Kang JL，Lee HS，Pack IS，et al. Phosphoinositide 3-kinase activity leads to silica-induced NF-κB activation through interacting with tyrosine-phosphorylated IκB-α and contributing to tyrosine phosphorylation of p65 NF-κB [J]. Mol Cell Biochem，2003，248（1/2）：17-24.
[28] Mackay F，Majeau GR，Hochman PS，et al. Lymphotoxin beta receptor triggering induces activation of the nuclear factor kappaB transcription factor in some cell types [J]. J Biol Chem，1996，271（40）：24934-24938.
[29] Zhao C，Li Z，Ji L，et al. PI3K-Akt signal transduction molecules maybe involved in downregulation of erythroblasts apoptosis and perifosine increased its apoptosis in chronic mountain sickness [J]. Med Sci Monit，2017，23：5637-5649.
[30] Binder D，van den Broek MF，Kagi D，et al. Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus [J]. J Exp Med，1998，187（11）：1903-1920. |
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