[1]李超然,闫 蕾,王 惠,等.炎性细胞因子对肺血管内皮细胞与肺成纤维细胞三维立体培养基质金属蛋白酶2的影响[J].陕西医学杂志,2023,52(7):920-924.[doi:DOI:10.3969/j.issn.1000-7377.2023.07.033]
　LI Chaoran,YAN Lei,WANG Hui,et al.Effect of inflammatory cytokines on MMP2 in three-dimensional culture of pulmonary vascular endothelial cells and lung fibroblasts[J].,2023,52(7):920-924.[doi:DOI:10.3969/j.issn.1000-7377.2023.07.033]
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炎性细胞因子对肺血管内皮细胞与肺成纤维细胞三维立体培养基质金属蛋白酶2的影响
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年7期
页码:
920-924
栏目:
临床病理
出版日期:
2023-07-05

文章信息/Info

Title:
Effect of inflammatory cytokines on MMP2 in three-dimensional culture of pulmonary vascular endothelial cells and lung fibroblasts
作者:
李超然1; 闫 蕾1; 王 惠1; 王学锷1; 芦 莎1; 谢琳霞1; 王 青1; 朱运奎1; 于 军2; Ronald F Ertl3(美国)
(1.西安国际医学中心医院呼吸与危重症医学三科,陕西 西安 710100; 2.西安国际医学中心医院临床实验中心,陕西 西安 710100; 3.美国内布拉斯加州大学医学中心重症医学部,内布拉斯加州 奥马哈 72662)
Author(s):
LI Chaoran; YAN Lei; WANG Hui; WANG Xue'e; LU Sha; XIE Linxia; WANG Qing; ZHU Yunkui; YU Jun; Ronald F Ertl
(The Third Department of Respiratory and Critical Care Medicine,Xi'an International Medical Center Hospital,Xi'an 710100,China)
关键词:
急性肺损伤;  细胞因子风暴;  基质金属蛋白酶;  三维立体培养;  肺成纤维细胞;  肺微血管内皮细胞
Keywords:
Acute lung injury;  Cytokine storm;  Matrix metalloproteinase;  Three-dimensional culture;  Lung fibroblasts;  Pulmonary microvascular endothelial cells
分类号:
R 562
DOI:
DOI:10.3969/j.issn.1000-7377.2023.07.033
文献标志码:
A
摘要:
目的:探讨炎性细胞因子在肺损伤和肺纤维化过程中与基质金属蛋白酶(MMPs)的相关性。方法: 建立肺微血管内皮细胞(HPMEC)/肺成纤维细胞(HFL)+Ⅰ型胶原三维立体培养模型,以不同细胞因子刺激,采用明胶酶谱法检测MMP2的活性,观察组肺细胞分泌MMP2,各种细胞因子与MMP2之间,以及各细胞因子之间的相互作用。结果:HFL是产生MMP2的主要细胞,在白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和中性粒细胞弹性蛋白酶(NE)的刺激下产生更多的MMP2,白细胞介素-6(IL-6)不诱导HFL产生MMP2,HPMEC只能产生极微量的MMP2,且各种细胞因子均不能诱导HPMEC产生更多MMP2。HFL与HPMEC混合三维立体培养下,TNF-α、IL-1β、NE能诱导产生多量的MMP2。结论: 在HFL与HPMEC混合3D培养条件下,炎性细胞因子TNF-α、IL-1β和NE可以诱导肺成纤维细胞产生大量MMP2,参与肺泡基质的降解损伤和致纤维化过程,IL-6不诱导MMP2产生,它可能通过诱导IL-1β和TNF-α的生成起作用。
Abstract:
Objective:To investigate the correlation between inflammatory cytokines and matrix metalloproteinases(MMPs)during lung injury and pulmonary fibrosis.Methods:The three-dimensional culture model of human pulmonary mircovascular endothelia cells(HPMEC)/Human fetal lung fibroblasts(HFL)+type Ⅰcollagen was established.The activity of MMP2 was detected by gelatin enzyme assay with different cytokine stimulation.The secretion of MMP2 by lung cells and the interaction between various cytokines and MMP2,as well as among various cytokines were observed.Results:HFL was the main cells producing MMP2,they produced more MMP2 when stimulated by IL-1β,TNF-α and neutrophil elastase(NE).However,IL-6 could not induce HFL to produce MMP2.HPMEC can only produce a very small amount of MMP2,and various cytokines can not induce HPMEC to produce more MMP2.In three-dimensional culture of HFL and HPMEC,TNF-α,IL-1β and NE can induce more MMP2.Conclusion:Inflammatory cytokines TNF-α,IL-1β and NE can induce lung fibroblasts to produce a large amount of MMP2,which is involved in the degradation and damage of alveolar matrix and fibrosis.IL-6 does not induce the production of MMP2,but it may act by inducing the production of IL-1β and TNF-α.

参考文献/References:

[1] Karki R,Sharma BR,Tuladhar S,et al.Synergism of TNF-α and IFN-γ triggers inflammatory cell death,tissue damage,and mortality in SARS-CoV-2 infection and cytokine shock syndromes[J].Cell,2021,184(1):149-168.
[2] Basheer M,Saad E,Kananeh M,et al.Cytokine patterns in COVID-19 patients:Which cytokines predict mortality and which protect against?[J].Curr Issues Mol Biol,2022,44(10):4735-4747.
[3] Ng WH,Tang PCH,Mahalingam S,et al.Repurposing of drugs targeting the cytokine storm induced by SARS-CoV-2[J].Brit J Pharmacol,2023,180(2):133-143.
[4] Kulanthaivel S,Kaliberdenko VB,Balasundaram K,et al.Tocilizumab in SARS-CoV-2 patients with the syndrome of cytokine storm:A narrative review[J].Rev Recent Clin Tria,2021,16(2):138-145.
[5] Leisman DE,Ronner L,Pinotti R,et al.Cytokine elevation in severe and critical COVID-19:A rapid systematic review,meta-analysis,and comparison with other inflammatory syndromes[J].Lancet Respir Med,2020,8(12):1233-1244.
[6] Chen R,Lan Z,Ye J,et al.Cytokine storm:The primary determinant for the pathophysiological evolution of COVID-19 deterioration[J].Front Immunol,2021,12:589095.
[7] 中国研究型医院学会危重症医学专业委员会,中国医药教育协会重症医学委员会.西维来司他纳临床应用专家共识[J].中国研究型医院,2022,9(1):9-13.
[8] Cokluk E,Doanay S,Ramazan-Sekerolu M,et al.Investigation of the effect of melatonin administration on inflammatory mediators MMP-2,TGF-β and VEGF levels in rats with sepsis[J].Int J Clin Pract,2021,75(11):e14832.
[9] Jones TK,Reilly JP,Anderson BJ,et al.Elevated plasma levels of matrix Metalloproteinase-3 and tissue-inhibitor of matrix metalloproteinases-1 associate with organ dysfunction and mortality in sepsis[J].Shock,2022,57(1):41-47.
[10] Fiotti N,Mearelli F,Di-Girolamo FG,et al.Genetic variants of matrix metalloproteinase and sepsis:The need speed study[J].Biomolecules,2022,12(2):279-284.
[11] Serrano-Gomez S,Burgos-Angulo G,Nino-Vargas DC,et al.Predictive value of matrix metalloproteinases and their inhibitors for mortality in septic patients:A cohort study[J].J Intensive Care Med,2020,35(1):95-103.
[12] Feng L,Liu Y,Chen M,et al.Matrix metalloproteinase 14 and plasma kallikrein 1 may be potential biomarkers in the diagnosis and treatment of sepsis:A proteomics and bioinformatics analysis[J].Zhonghua Wei Zhong Bing Ji Jiu Yi Xue,2022,34(7):676-681.
[13] 佘育纯,路 勇,王建龙.血清基质金属蛋白酶-9、二胺氧化酶、Toll样受体9与急性胰腺炎患者疾病严重程度及肠黏膜屏障损伤相关性分析[J].陕西医学杂志,2023,52(3):292-296.
[14] Mohammadi A,Balan I,Yadav S,et al.Post-COVID-19 pulmonary fibrosis[J].Cureus, 2022,14(3):e22770.
[15] 梁 红,霍红艳.右美托咪定对盲肠结扎穿孔术诱导的脓毒症大鼠急性肺损伤保护作用及其与磷酸化JAK激酶2/酪氨酸磷酸化通路的关系[J].陕西医学杂志,2023,52(1):12-17.
[16] Zhu YK,Liu X,Wang H,et al.Interactions between monocytes and smooth-muscle cells can lead to extracellular matrix degradation[J].J Allergy Clin Immunol Dec,2001,108(6):989-996.
[17] 甘世伟,章晓红,陈 红.白介素6与冠状病毒肺炎关系的研究进展[.J].中华临床医师杂志,2020,14(7):573-576.
[18] Hama-Amin BJ,Kakamad FH,Ahmed GS,et al.Post COVID-19 pulmonary fibrosis:A meta-analysis study[J].Ann Med Surg(Lond),2022,77:103590.
[19] Bormann T,Maus R,Stolper J,et al.Role of matrix metalloprotease-2 and MMP-9 in experimental lung fibrosis in mice[J].Respir Res,2022,23(1):180.
[20] Chuliá-Peris L,Carreres-Rey C,Gabasa M,et al.Matrix metalloproteinases and their inhibitors in pulmonary fibrosis:EMMPRIN/CD147 comes into play[J].Int J Mol Sci,2022,23(13):6894.

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备注/Memo

备注/Memo:
基金项目:陕西省科技计划项目(2018ZDXM-SF-068)
更新日期/Last Update: 2023-07-05