IL-15及其受体在HIV感染中表达及意义
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摘要
目的研究人免疫缺陷病毒(HIV)感染者外周血单个核细胞(PBMC)中白细胞介素15(IL-15)、白细胞介素15受体α(IL-15Rα)及解聚素-金属蛋白酶17(ADAM17)mRNA的表达,探讨其在HIV感染疾病进展中的作用。方法应用实时定量PCR(RT-PCR)检测9例HIV早期感染者(感染<1年,EHI组)、30例慢性HIV感染者(感染≥1年,CHI组)及9例健康对照(NC组)PBMC中IL-15、IL-15Rα、ADAM-17 mRNA水平。结果 CHI组PBMC中IL-15 mRNA的表达明显高于NC组(P<0.01);EHI组及CHI组PBMC中IL-15Rα、ADAM17 mRNA的表达明显高于NC组(P<0.05);HIV感染者PBMC中IL-15、IL-15Rα、ADAM17 mRNA的表达与病毒载量(VL)呈正相关(P<0.05); HIV感染者IL-15 mRNA表达与IL-15RαmRNA表达呈正相关(P<0.001), IL-15RαmRNA表达与ADAM17mRNA表达水平呈正相关(P<0.001)。结论 HIV感染后IL-15、IL-15Rα、ADAM17表达上调,皆与HIV病毒复制水平相关。
Objective To study expressions of interleukin-15(IL-15), interleukin-15 receptor α(IL-15 Rα) and a disintegrin and metalloprotease domain 17(ADAM 17) in peripheral blood mononuclear cells(PBMC) from HIV-infected individuals and to explore roles of the expressions in the progression of HIV infection. Methods Reverse transcription-PCR(RT-PCR) was used to detect IL-15, IL-15 Rα and ADAM 17 mRNA in PBMC of 9 early HIV-infected individuals(infected within one year, EHI group), 30 chronic HIV-infected individuals(infected for more than one year, CHI group), and 9 healthy controls(NC group). Results The expression of IL-15 mRNA in PBMC of CHI group was significantly higher than that in NC group(P < 0.01). The expression of IL-15 Ra and ADAM 17 mRNA in PBMC of EHI group and CHI group was significantly higher than those in NC group(both P< 0.05). The expression of IL-15, IL-15 Ra and ADAM 17 mRNA in PBMC of HIV-infected individuals were positively correlated with viral load(VL)(P< 0.05). IL-15 mRNA expression in PBMC was positively correlated with IL-15 Rα mRNA expression in HIV-infected individuals(P < 0.001), and IL-15 Ra mRNA expression was positively correlated with ADAM 17 mRNA expression(P< 0.001). Conclusion HIV-infection increases the expression of IL-15, IL-15 Rα, and ADAM 17 in PBMCs and their expressions are related to HIV viral load in HIV-infected individuals.
Objective To study expressions of interleukin-15(IL-15), interleukin-15 receptor α(IL-15 Rα) and a disintegrin and metalloprotease domain 17(ADAM 17) in peripheral blood mononuclear cells(PBMC) from HIV-infected individuals and to explore roles of the expressions in the progression of HIV infection. Methods Reverse transcription-PCR(RT-PCR) was used to detect IL-15, IL-15 Rα and ADAM 17 mRNA in PBMC of 9 early HIV-infected individuals(infected within one year, EHI group), 30 chronic HIV-infected individuals(infected for more than one year, CHI group), and 9 healthy controls(NC group). Results The expression of IL-15 mRNA in PBMC of CHI group was significantly higher than that in NC group(P < 0.01). The expression of IL-15 Ra and ADAM 17 mRNA in PBMC of EHI group and CHI group was significantly higher than those in NC group(both P< 0.05). The expression of IL-15, IL-15 Ra and ADAM 17 mRNA in PBMC of HIV-infected individuals were positively correlated with viral load(VL)(P< 0.05). IL-15 mRNA expression in PBMC was positively correlated with IL-15 Rα mRNA expression in HIV-infected individuals(P < 0.001), and IL-15 Ra mRNA expression was positively correlated with ADAM 17 mRNA expression(P< 0.001). Conclusion HIV-infection increases the expression of IL-15, IL-15 Rα, and ADAM 17 in PBMCs and their expressions are related to HIV viral load in HIV-infected individuals.
引文
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[11] Ring AM, Lin JX, Feng D, et al. Mechanistic and structural insight into the functional dichotomy between interleukin-2 and interleukin-15[J]. Nature Immunology, 2012,13(12):1187-1195.
[12] Bouchaud G, Garrigue-Antar L, Sole V, et al. The exon-3-encoded domain of IL-15 alpha ralpha contributes to IL-15 high-affinity binding and is crucial for the IL-15 antagonistic effect of soluble IL-15ralpha[J]. J Mol Biol, 2008, 382(1):1-12.
[13] Rubinstein MP, Kovar M, Purton JF, et al. Converting IL-15 to a superagonist by binding to soluble IL-15r[J]. Proc Natl Acad Sci USA, 2006, 103(24):9166-9171.
[14] Park JY, Ligons DL, Park JH. Out-sourcing for trans-presentation:assessing T cell intrinsic and extrinsic IL-15 expression with IL-15gene reporter mice[J]. Immune Netw, 2018, 18(1):e13.
[2]周金玲,王莉,周丹,等.辽宁省1993—2015年艾滋病病例特征分析[J].中国公共卫生,2017, 33(8):1209-1212.
[3]Bergamaschi C, Kulkami V, Rosati M, et al. Intramuscular delivery of heterodimeric il-15 DNA in macaques produces systemic levels of bioactive cytokine inducing proliferation of NK and T cells[J].Gene Therapy, 2015, 22(1):76-86.
[4]Yan I, Schwarz J, Lücke K, et al. ADAM 17 controls IL-6 signaling by cleavage of the murine IL-6Ra from the cell surface of leukocytes during inflammatory responses[J]. Journal of Leukocyte Biology, 2015,99(5):749-760.
[5]Anthony SM, Howard ME, Hailemichael Y, et al. Soluble interleukin-15 complexes are generated in vivo by typeⅠinterferon dependent and independent pathways[J]. PLoS One, 2015, 10(3):e0120274.
[6]Ahmad R, Sindhu ST, Toma E, et al. Studies on the production of IL-15 in HIV-infected/AIDS patients[J]. J Clin Immunol, 2003,23(2):81-90.
[7]Swaminathan S, Qiu J, Rupert AW, et al. Interleukin-15(IL-15)strongly correlates with increasing HIV-1 viremia and markers of inflammation[J]. PLoS One, 2016, 11(11):e0167091.
[8] Wang Y, Bai Y, Li Y, et al. IL-15 enhances activation and IGF-1production of dendritic epidermal T cells to promote wound healing in diabetic mice[J]. Frontiers in Immunology, 2017,8:1557.
[9] Bastidas S, Graw F, Smith MZ, et al. Cd8+T cells are activated in an antigen-independent manner in HIV-infected individuals[J]. The Journal of Immunology, 2014, 192(4):1732-1744.
[10] Wherry EJ. T cell exhaustion[J]. Nat Immunol, 2011, 12(6):492-499.
[11] Ring AM, Lin JX, Feng D, et al. Mechanistic and structural insight into the functional dichotomy between interleukin-2 and interleukin-15[J]. Nature Immunology, 2012,13(12):1187-1195.
[12] Bouchaud G, Garrigue-Antar L, Sole V, et al. The exon-3-encoded domain of IL-15 alpha ralpha contributes to IL-15 high-affinity binding and is crucial for the IL-15 antagonistic effect of soluble IL-15ralpha[J]. J Mol Biol, 2008, 382(1):1-12.
[13] Rubinstein MP, Kovar M, Purton JF, et al. Converting IL-15 to a superagonist by binding to soluble IL-15r[J]. Proc Natl Acad Sci USA, 2006, 103(24):9166-9171.
[14] Park JY, Ligons DL, Park JH. Out-sourcing for trans-presentation:assessing T cell intrinsic and extrinsic IL-15 expression with IL-15gene reporter mice[J]. Immune Netw, 2018, 18(1):e13.