Role of sulforaphane in the MUC5AC mucin production of A549 cell_Chinese Journal of Evidence-Based Medicine

Authors：

LIN Xiaoping ,  ZENG Yiming

Department of Respiratory Medicine, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, P.R.China;

Corresponding author：

ZENG Yiming, Email: zeng_yi_ming@126.com

Keywords：

Sulforaphane; Mucus; MUC5AC; Nrf2 signaling pathway; Heme oxygenase-1

DOI：

10.7507/1672-2531.201605024

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the role of sulforaphane (SFN) on the regulation of airway mucin 5AC mucin expression in the airway epithelial cell line (A549), and the underlying mechanism. Methods The experiments were performed in culture of PMA and H₂O₂ induced A549 in vitro. A549 cells divided into three groups: the control group, the model group (PMA and H₂O₂) and the intervention groups (SFN+PMA; SFN+H₂O₂). The intervention group's cells were pretreated with SFN for 30 mins before exposure to stimuli (PMA or H₂O₂). The MUC5AC, Nrf2 and the antioxidant gene HO-1, NQO1, GCLC mRNA levels were analyzed by real time-PCR, and protein production was assayed by western blot. Results Compared with the control group, expression of MUC5AC mucin was increased after being stimulated by PMA or H₂O₂ (P<0.05), but it was significantly inhibited by SFN (P<0.05). SFN induced the expression of Nrf2 gene and the antioxidant gene HO-1 (compared with the control and model groups,P<0.05). Conclusion Sulforaphane involves the airway mucous hypersecretion induced by PMA and H₂O₂, and Nrf2/HO-1 signaling pathway may play an important role in mucin MUC5AC regulation.

Citation： LIN Xiaoping, ZENG Yiming. Role of sulforaphane in the MUC5AC mucin production of A549 cell. Chinese Journal of Evidence-Based Medicine, 2017, 17(1): 26-32. doi: 10.7507/1672-2531.201605024 Copy

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9.	Lu MC, Ji JA, Jiang ZY,et al. The Keap1-Nrf2-ARE Pathway As a Potential Preventive and Therapeutic Target: An Update. Med Res Rev, 2016, 36(5): 924-963.
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14.	Kalpana Deepa Priya D, Gayathri R, Sakthisekaran D. Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in vivo by modulating the metabolic activation and detoxification of benzo(a)pyrene. Biomed Pharmacother, 2011, 65(1): 9-16.
15.	Pekovic-Vaughan V, Gibbs J, Yoshitane H,et al. The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis. Genes Dev, 2014, 28(6): 548-560.
16.	Hewson CA, Edbrooke MR, Johnston SL. PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J Mol Biol, 2004, 344(3): 683-695.
17.	Choi JH, Jin SW, Kim HG,et al. Saponins, especially platyconic acid A, from Platycodon grandiflorum reduce airway inflammation in ovalbumin-induced mice and PMA-exposed A549 cells. J Agric Food Chem, 2015, 63(5): 1468-1476.
18.	Qi T, Xu F, Yan X,et al. Sulforaphane exerts anti-inflammatory effects against lipopolysaccharide-induced acute lung injury in mice through the Nrf2/ARE pathway. Int J Mol Med, 2016, 37(1): 182-188.
19.	Brown RH, Reynolds C, Brooker A,et al. Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways. Respir Res, 2015, 16:106.
20.	Harvey CJ, Thimmulappa RK, Sethi S,et al. Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model. Sci Transl Med, 2011, 3(78): 78ra32.
21.	Yuan S, Hollinger M, Lachowicz-Scroggins ME,et al. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels. Sci Transl Med, 2015, 7(276): 276ra27.
22.	包爱华, 陈宇清, 张旻, 等. 臭氧氧化应激对小鼠急性过敏性气道炎症所致气道高反应性和黏液分泌的影响. 中华结核和呼吸病学杂志, 2015, 53(4): 137-148.
23.	Qi L, Xiangdong Z, Hongmei Y,et al. Regulation of neutrophil elastase-induced MUC5AC expression by nuclear factor erythroid-2 related factor 2 in human airway epithelial cells. J Investig Med, 2010, 58(5): 730-736.

1. Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med, 2010, 363(23): 2233-2247.
2. Curran DR, Cohn L. Advances in mucous cell metaplasia: a plug for mucus as a therapeutic focus in chronic airway disease. Am J Respir Cell Mol Biol, 2010, 42(3): 268-275.
3. Cerveri I, Brusasco V. Revisited role for mucus hypersecretion in the pathogenesis of COPD. Eur Respir Rev, 2010, 19(116): 109-112.
4. Jinnai M, Niimi A, Ueda T,et al. Induced sputum concentrations of mucin in patients with asthma and chronic cough. Chest, 2010, 137(5): 1122-1129.
5. Shao MX, Nadel JA. Neutrophil elastase induces MUC5AC mucin production in human airway epithelial cells via a cascade involving protein kinase C, reactive oxygen species, and TNF-alpha-converting enzyme. J Immunol, 2005, 175(6): 4009-4016.
6. Yan F, Li W, Jono H,et al. Reactive oxygen species regulate Pseudomonas aeruginosa lipopolysaccharide- induced MUC5AC mucin expression via PKC-NADPH oxidase-ROS- TGF-a signaling pathways in human airway epithelial cells. Biochem Biophys Res Commun, 2008, 366(2): 51351-51359.
7. Al-Sawaf O, Clarner T, Fragoulis A,et al. Nrf2 in health and disease: current and future clinical implications. Clin Sci (Lond), 2015, 129(12): 989-999.
8. Huang Y, Li W, Su ZY,et al. The complexity of the Nrf2 pathway: beyond the antioxidant response. J Nutr Biochem, 2015, 26(12): 1401-1413.
9. Lu MC, Ji JA, Jiang ZY,et al. The Keap1-Nrf2-ARE Pathway As a Potential Preventive and Therapeutic Target: An Update. Med Res Rev, 2016, 36(5): 924-963.
10. Ying YH, Lin XP, Zhou HB,et al. Nuclear erythroid 2 p45-related factor-2 Nrf2 ameliorates cigarette smoking-induced mucus overproduction in airway epithelium and mouse lungs. Microbes Infect, 2014, 16(10): 855-863.
11. Juge N, Mithen RF, Traka M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci, 2007, 64(9): 1105-1127.
12. Myzak MC, Dashwood RH. Chemoprotection by sulforaphane: keep one eye beyond Keap1. Cancer Lett, 2006, 233(2): 208-218.
13. Hong Y, Yan W, Chen S,et al. The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice. Acta Pharmacol Sin, 2010, 31(11): 1421-1430.
14. Kalpana Deepa Priya D, Gayathri R, Sakthisekaran D. Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in vivo by modulating the metabolic activation and detoxification of benzo(a)pyrene. Biomed Pharmacother, 2011, 65(1): 9-16.
15. Pekovic-Vaughan V, Gibbs J, Yoshitane H,et al. The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis. Genes Dev, 2014, 28(6): 548-560.
16. Hewson CA, Edbrooke MR, Johnston SL. PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J Mol Biol, 2004, 344(3): 683-695.
17. Choi JH, Jin SW, Kim HG,et al. Saponins, especially platyconic acid A, from Platycodon grandiflorum reduce airway inflammation in ovalbumin-induced mice and PMA-exposed A549 cells. J Agric Food Chem, 2015, 63(5): 1468-1476.
18. Qi T, Xu F, Yan X,et al. Sulforaphane exerts anti-inflammatory effects against lipopolysaccharide-induced acute lung injury in mice through the Nrf2/ARE pathway. Int J Mol Med, 2016, 37(1): 182-188.
19. Brown RH, Reynolds C, Brooker A,et al. Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways. Respir Res, 2015, 16:106.
20. Harvey CJ, Thimmulappa RK, Sethi S,et al. Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model. Sci Transl Med, 2011, 3(78): 78ra32.
21. Yuan S, Hollinger M, Lachowicz-Scroggins ME,et al. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels. Sci Transl Med, 2015, 7(276): 276ra27.
22. 包爱华, 陈宇清, 张旻, 等. 臭氧氧化应激对小鼠急性过敏性气道炎症所致气道高反应性和黏液分泌的影响. 中华结核和呼吸病学杂志, 2015, 53(4): 137-148.
23. Qi L, Xiangdong Z, Hongmei Y,et al. Regulation of neutrophil elastase-induced MUC5AC expression by nuclear factor erythroid-2 related factor 2 in human airway epithelial cells. J Investig Med, 2010, 58(5): 730-736.

Chinese Journal of Evidence-Based Medicine

Role of sulforaphane in the MUC5AC mucin production of A549 cell

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