IL-1β通过p38、JNK和NF-κB信号通路促进髓核细胞增殖-东南大学学报医学版

IL-1β通过p38、JNK和NF-κB信号通路促进髓核细胞增殖

单位：1. 东南大学医学院, 江苏南京 210009;
2. 东南大学附属中大医院脊柱外科中心, 江苏南京 210009

分类号：R329.28

出版年·卷·期（页码）：2016·35·第一期（32-36）

摘要：

目的:探讨白细胞介素1β(IL-1β)对髓核细胞增殖的影响,并深入研究其机制。方法:体外培养人髓核细胞,用IL-1β处理髓核细胞,通过CCK-8实验和Ki67免疫荧光实验检测IL-1β对髓核细胞增殖能力的影响。用Western blotting检测IL-1β对MAPK和NF-κB信号通路的影响。通过对细胞信号通路进行特异性抑制,观察上述通路在IL-1β作用于髓核细胞过程中的作用。结果:CCK-8实验和Ki67免疫荧光实验均提示IL-1β提高髓核细胞的增殖能力。Western blotting实验显示IL-1β显著激活髓核细胞中的MAPK和NF-κB信号通路。使用p38、JNK和NF-κB的抑制剂均能明显抑制IL-1β诱导的髓核细胞增殖,而ERK的抑制剂则不能。结论:IL-1β通过p38、JNK和NF-κB信号通路促进髓核细胞增殖。

Objective:To investigate the effect of IL-1β on proliferation of human nucleus pulposus(NP) cells.Methods:NP cells were treated with IL-1β.Cell proliferation was determined by CCK-8 analysis and Ki67 immunofluorescence staining.To identify the mechanism by which IL-1β induced proliferation of NP cells,Western blotting was carried out and selective inhibitors of MAPK and NF-κB signaling pathways were used.Results:Treatment with IL-1β increased cell viability (as determined by CCK-8 analysis) and the number of Ki67-positive NP cells. IL-1β activated MAPK and NF-κB signaling pathways in NP cells. Moreover,inhibition of p38,JNK and NF-κB blocked IL-1β-stimulated proliferation of NP cells. Conclusion:The current findings suggest that the effect of IL-1β on intervertebral disc degeneration involves promotion of the proliferation of human NP cells via the p38,JNK and NF-κB pathways.

参考文献：

[1] WADDELL G.Low back pain:a twentieth century health care enigma[J].Spine (Phila Pa 1976),1996,21(24):2820-2825.
[2] DAGENAIS S,CARO J,HALDEMAN S.A systematic review of low back pain cost of illness studies in the United States and internationally[J].Spine J,2008,8(1):8-20.
[3] JOUD A,PETERSSON I F,ENGLUND M.Low back pain:epidemiology of consultations[J].Arthritis Care Res (Hoboken),2012,64(7):1084-1088.
[4] MAROUDAS A,STOCKWELL R A,NACHEMSON A,et al.Factors involved in the nutrition of the human lumbar intervertebral disc:cellularity and diffusion of glucose in vitro[J].J Anat,1975,120(Pt 1):113-130.
[5] ISHⅡ T,TSUJI H,SANO A,et al.Histochemical and ultrastructural observations on brown degeneration of human intervertebral disc[J].J Orthop Res,1991,9(1):78-90.
[6] HASTREITER D,OZUNA R M,SPECTOR M.Regional variations in certain cellular characteristics in human lumbar intervertebral discs,including the presence of alpha-smooth muscle actin[J].J Orthop Res,2001,19(4):597-604.
[7] JOHNSON W E,EISENSTEIN S M,ROBERTS S.Cell cluster formation in degenerate lumbar intervertebral discs is associated with increased disc cell proliferation[J].Connect Tissue Res,200142(3):197-207.
[8] NOMURA T,MOCHIDA J,OKUMA M,et al.Nucleus pulposus allograft retards intervertebral disc degeneration[J].Clin Orthop Relat Res,2001,389:94-101.
[9] SAKAI D,MOCHIDA J,YAMAMOTO Y,et al.Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc:a potential therapeutic model for disc degeneration[J].Biomaterials,2003,24(20):3531-3541.
[10] PHILLIPS K L,CULLEN K,CHIVERTON N,et al.Potential roles of cytokines and chemokines in human intervertebral disc degeneration:interleukin-1 is a master regulator of catabolic processes[J].Osteoarthritis Cartilage,2015,23(7):1165-1177.
[11] ZIELENIEWSKI W,ZIELENIEWSKI J,STEPIEN H.Interleukin-1 beta,but not IL-1 alpha,stimulates cell proliferation in the adrenal cortex[J].Cytobios,1995,84(338-339):199-204.
[12] DAVIS R,PILLAI S,LAWRENCE N,et al.TNF-alpha-mediated proliferation of vascular smooth muscle cells involves Raf-1-mediated inactivation of Rb and transcription of E2F1-regulated genes[J].Cell Cycle,2012,11(1):109-118.
[13] BLANCO F J,GENG Y,LOTZ M.Differentiation-dependent effects of IL-1 and TGF-beta on human articular chondrocyte proliferation are related to inducible nitric oxide synthase expression[J].J Immunol,1995,154(8):4018-4026.
[14] 王小虎,吴小涛.椎间盘退变机制的研究概况[J].东南大学学报:医学版,2011,30(5):778-783.
[15] 范宇栋,吴小涛.退变椎间盘细胞细胞因子分泌的改变及其影响[J].东南大学学报:医学版,2014,33(3):372-375.
[16] le MAITRE C L,FREEMONT A J,HOYLAND J A.The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration[J].Arthritis Res Ther,2005,7(4):R732-745.
[17] JIMBO K,PARK J S,YOKOSUKA K,et al.Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro[J].J Neurosurg Spine,2005,2(5):589-595.
[18] SHEN B,MELROSE J,GHOSH P,et al.Induction of matrix metalloproteinase-2 and-3 activity in ovine nucleus pulposus cells grown in three-dimensional agarose gel culture by interleukin-1beta:a potential pathway of disc degeneration[J].Eur Spine J,2003,12(1):66-75.
[19] TIAN Y,YUAN W,FUJITA N,et al.Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1(ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-kappaB[J].Am J Pathol,2013,182(6):2310-2321.
[20] ZHANG C C,ZHOU J S,HU J G,et al.Effects of IGF-1 on IL-1beta-induced apoptosis in rabbit nucleus pulposus cells in vitro[J].Mol Med Rep,2013,7(2):441-444.
[21] JIANG L,JIN Y,WANG H,et al.Glucosamine protects nucleus pulposus cells and induces autophagy via the mTOR-dependent pathway[J].J Orthop Res,2014,32(11):1532-1542.
[22] YANG S D,YANG D L,SUN Y P,et al.17beta-estradiol protects against apoptosis induced by interleukin-1beta in rat nucleus pulposus cells by down-regulating MMP-3 and MMP-13[J].Apoptosis,2015,20(3):348-357.
[23] WANG H,TIAN Y,WANG J,et al.Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells:implications in intervertebral disc degeneration[J].J Biol Chem,2013,288(23):16761-16774.
[24] WANG X H,HONG X,ZHU L,et al.Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-kappaB,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase[J].Exp Biol Med (Maywood),2015,240(4):411-417.
[25] WANG X,WANG H,YANG H,et al.Tumor necrosis factor-alpha-and interleukin-1beta-dependent matrix metalloproteinase-3 expression in nucleus pulposus cells requires cooperative signaling via syndecan 4 and mitogen-activated protein kinase-NF-kappaB axis:implications in inflammatory disc disease[J].Am J Pathol,2014,184(9):2560-2572.

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