The effects of elafin on the regulation of mucin5AC in airway epithelial cells_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LIU Feng ¹ ,  ZHOU Xiangdong ¹ , YU Hongmei ² , LI Qi ¹ , ZHONG Youqing ¹

1. Department of Respiratory Medicine, First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P. R. China;
2. Department of Respiratory Medicine, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China;

Corresponding author：

ZHOU Xiangdong, Email: zxd999@263.net

Keywords：

Elafin; Epithelial cells; Mucin5AC; Airway mucous hypersecretion

DOI：

10.7507/1671-6205.201711009

Video：

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ObjectiveTo explore the effects of elafin on the regulation of mucin5AC (MUC5AC) in airway epithelial cells.MethodsAfter cultivating epithelial cells in vitro, cells were stimulated by cigarette smoke extract (CSE) and lipopolysaccharide (LPS), the intracellular MUC5AC production and extracellular secretion were assayed by immunofluorescence and ELISA, respectively.ResultsThe level of MUC5AC protein was obviously increased in the LPS stimulation group [(0.785±0.005) μg/ml vs. (0.232±0.004) μg/ml] and the CSE stimulation group [(0.803±0.005) μg/ml vs. (0.255±0.003) μg/ml] than those in the blank control groups (both P<0.01). When pretreated with elafin then stimulated by LPS and CSE, the MUC5AC productions were evidently decreased than those in the single LPS and CSE stimulation groups [(0.363±0.003) μg/ml and (0.406±0.006) μg/ml, bothP<0.01]. As compared with the blank control groups, the MUC5AC protein secretion were significantly decreased after stimulated with single elafin [(0.176±0.002) μg/ml and (0.193±0.004) μg/ml, bothP<0.05].ConclusionElafin may inhibit MUC5AC hypersecretion by blocking MUC5AC production and secretion.

Citation： LIU Feng, ZHOU Xiangdong, YU Hongmei, LI Qi, ZHONG Youqing. The effects of elafin on the regulation of mucin5AC in airway epithelial cells. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(3): 296-300. doi: 10.7507/1671-6205.201711009 Copy

1.	徐晓艳, 周向东. 细胞外信号调节激酶信号通路在中性粒细胞弹性蛋白酶介导气道黏液高分泌中的作用. 中国呼吸与危重监护杂志, 2005, 4(6): 468.
2.	王晓龙, 周向东. 核转录因子-κB 在慢性气道粘液高分泌大鼠肺组织中的表达及意义. 中国呼吸与危重监护杂志, 2004, 3(2): 101-102.
3.	Li Q, Zhou XD, Yu HM, et al. Regulation of neutrophil elastase-induced MUC5AC expression by nuclear factor erythroid-2 related factor 2 in human airway epithelial cells. J lnvestig Med, 2010, 58(5): 730-736.
4.	Butler Mw, Robertson I, Greene CM, et al. Elafin prevents lipopolysaccharide-induced AP-1 and NF-kappaB activation via an effect on the ubiquitin-proteasome pathway. J Biol Chem, 2006, 281(46): 34730-34735.
5.	Baginski TK, Dabbagh K, Satjawatcharaphong C, et al. Cigarette smoke synergistically enhances respiratory mucin induction by proinflammatory stimuli. Am J Respir Cell Mol Biol, 2006, 35 (2): 165-174.
6.	Desterro JM, Rodriguez MS, Hay RT. SUMO-1 modification of lkappaBalpha inhibits NF-kappaB activation. Mol Cell, 1998, 2(2): 233-239.
7.	Fujisawa T, Velichko S, Thai P, et al. Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-kappaB paradigm. J Immunol, 2009, 183(10): 6236-6243.
8.	Ishimoto H, Mukae H, Sakamoto N, et al. Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin. J Antimicrob Chemother, 2009, 63(1): 109-114.
9.	杨捷, 周向东. 天然内生多肽 Elafin 真核表达载体的构建及其在真核细胞的表达. 中国抗生素杂志, 2005, 30(10): 608-610.
10.	Roghanian A, Sallenave JM. Neutrophil elastase(NE) and NE inhibitors: Canonical and noncanonical functions in lung chronic inflammatory diseases(cystic fibrosis and chronic obstructive pulmonary disease). J Aerosol Med Pulm Drug Deliv, 2008, 21(1): 125-144.
11.	杜先智, 周向东. 弹性蛋白酶特异性抑制因子 Elafin 基因重组腺病毒载体的构建、鉴定与表达. 中国免疫学杂志, 2007, 23(6): 495-499.
12.	杨捷, 周向东. 核转录因子-κB 在中性粒细胞弹力酶诱导肺 A549 细胞 Elafin 表达中的作用. 中国呼吸与危重监护杂志, 2004, 3(4): 245-247.
13.	Vandermeeren M, Daneels G, Bergers M. Development and application of monoclonal antibodies against SKALP/elafin and other trappin family members. Arch Dermatol Res, 2001, 293(7): 343-349.
14.	邓玥, 张婷, 周向东. Elafin 在气道炎症性疾病中的作用. 国际呼吸杂志, 2014, 34(20): 1576-1579.
15.	Sailenave JM, Shulmann J, Crossley J, et al. Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor(ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Am J Respir Cell Mol Biol, 1994, 11(6): 733-741.
16.	陈淑靖, 白春学. 气道黏液中黏蛋白 MUC5AC 的研究进展. 中华结核和呼吸杂志, 2007, 30 (6): 461-463.
17.	Kirkham S, Sheehan JK, Knight D, et al. Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B. Biochem J, 2002, 361(3): 537-546.
18.	余红梅, 李琪, Juliy M. 内生多肽 Elafin 对气道黏蛋白 5AC 表达的影响. 中华结核和呼吸杂志, 2010, 33(11): 801-805.
19.	Li Q, Zhou XD, Nie X, et al. The role of recombinant human elafin in the resistance of A549 cells against Pseudomonas aeruginosa biofilm. Respiration, 2010, 79(1): 68-75.

1. 徐晓艳, 周向东. 细胞外信号调节激酶信号通路在中性粒细胞弹性蛋白酶介导气道黏液高分泌中的作用. 中国呼吸与危重监护杂志, 2005, 4(6): 468.
2. 王晓龙, 周向东. 核转录因子-κB 在慢性气道粘液高分泌大鼠肺组织中的表达及意义. 中国呼吸与危重监护杂志, 2004, 3(2): 101-102.
3. Li Q, Zhou XD, Yu HM, et al. Regulation of neutrophil elastase-induced MUC5AC expression by nuclear factor erythroid-2 related factor 2 in human airway epithelial cells. J lnvestig Med, 2010, 58(5): 730-736.
4. Butler Mw, Robertson I, Greene CM, et al. Elafin prevents lipopolysaccharide-induced AP-1 and NF-kappaB activation via an effect on the ubiquitin-proteasome pathway. J Biol Chem, 2006, 281(46): 34730-34735.
5. Baginski TK, Dabbagh K, Satjawatcharaphong C, et al. Cigarette smoke synergistically enhances respiratory mucin induction by proinflammatory stimuli. Am J Respir Cell Mol Biol, 2006, 35 (2): 165-174.
6. Desterro JM, Rodriguez MS, Hay RT. SUMO-1 modification of lkappaBalpha inhibits NF-kappaB activation. Mol Cell, 1998, 2(2): 233-239.
7. Fujisawa T, Velichko S, Thai P, et al. Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-kappaB paradigm. J Immunol, 2009, 183(10): 6236-6243.
8. Ishimoto H, Mukae H, Sakamoto N, et al. Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin. J Antimicrob Chemother, 2009, 63(1): 109-114.
9. 杨捷, 周向东. 天然内生多肽 Elafin 真核表达载体的构建及其在真核细胞的表达. 中国抗生素杂志, 2005, 30(10): 608-610.
10. Roghanian A, Sallenave JM. Neutrophil elastase(NE) and NE inhibitors: Canonical and noncanonical functions in lung chronic inflammatory diseases(cystic fibrosis and chronic obstructive pulmonary disease). J Aerosol Med Pulm Drug Deliv, 2008, 21(1): 125-144.
11. 杜先智, 周向东. 弹性蛋白酶特异性抑制因子 Elafin 基因重组腺病毒载体的构建、鉴定与表达. 中国免疫学杂志, 2007, 23(6): 495-499.
12. 杨捷, 周向东. 核转录因子-κB 在中性粒细胞弹力酶诱导肺 A549 细胞 Elafin 表达中的作用. 中国呼吸与危重监护杂志, 2004, 3(4): 245-247.
13. Vandermeeren M, Daneels G, Bergers M. Development and application of monoclonal antibodies against SKALP/elafin and other trappin family members. Arch Dermatol Res, 2001, 293(7): 343-349.
14. 邓玥, 张婷, 周向东. Elafin 在气道炎症性疾病中的作用. 国际呼吸杂志, 2014, 34(20): 1576-1579.
15. Sailenave JM, Shulmann J, Crossley J, et al. Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor(ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Am J Respir Cell Mol Biol, 1994, 11(6): 733-741.
16. 陈淑靖, 白春学. 气道黏液中黏蛋白 MUC5AC 的研究进展. 中华结核和呼吸杂志, 2007, 30 (6): 461-463.
17. Kirkham S, Sheehan JK, Knight D, et al. Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B. Biochem J, 2002, 361(3): 537-546.
18. 余红梅, 李琪, Juliy M. 内生多肽 Elafin 对气道黏蛋白 5AC 表达的影响. 中华结核和呼吸杂志, 2010, 33(11): 801-805.
19. Li Q, Zhou XD, Nie X, et al. The role of recombinant human elafin in the resistance of A549 cells against Pseudomonas aeruginosa biofilm. Respiration, 2010, 79(1): 68-75.

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The effects of elafin on the regulation of mucin5AC in airway epithelial cells

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