사람 호흡기 상피세포에서 Peroxiredoxin 2에 의한 Lipopolysaccharide에 유도된점액 발현과 Reactive Oxygen Species 생성의 억제 = Peroxiredoxin 2 Inhibits Lipopolysaccharide Induced Mucin Expression and Reactive Oxygen Species Production in Human Airway Epithelial Cells

다국어 초록 (Multilingual Abstract)

Background and Objectives Peroxiredoxin (Prx) is an antioxidant enzyme involved in signalingpathway. Prx2 is the most abundant in mammalian gray matter neurons and has protectiverole under oxidative stress. MUC5AC and MUC5B are typical mucin genes in human airwayepithelial cells. Even if free radicals play a key role in chronic respiratory inflammatorydiseases, the effects of the Prx2 on mucin expression and oxidative stress are not clearly known.
The purpose of this study is to investigate the effect of Prx2 on lipopolysaccharide (LPS)-inducedMUC5AC/5B expression and reactive oxygen species (ROS) in human airway epithelialcells.
Subjects and Method In NCI-H292 cells and human nasal epithelial cells, the effects ofPrx2 on LPS-induced MUC5AC/5B expression and ROS production were investigated usingreverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, enzymelinked immunosorbent assay (ELISA) and flow cytometry analysis.
Results MUC5AC, MUC5B mRNA expression and protein production were increased byLPS. ROS production was also increased by LPS. Prx2 suppressed the LPS-induced MUC5ACmRNA expression and protein production as well as ROS production. However, Prx2 did notinhibit MUC5B mRNA expression and protein production. N-acetylcysteine, diphenyleneiodonium,and apocynin also inhibited LPS-induced ROS production.
Conclusion These results may show that Prx2 suppresses LPS-induced MUC5AC expressionvia ROS in human airway epithelial cells.

참고문헌 (Reference)

1 안지훈, "호흡기 상피세포에서 MUC5AC와 MUC5B 발현에 대한 다중벽 탄소나노튜브의 효과" 대한이비인후과학회 58 (58): 552-557, 2015

2 이영하, "사람 호흡기 상피세포에서 고농도 포도당 처치 후 활성산소를 통한 MUC5B 점액유전자 발현" 대한이비인후과학회 60 (60): 396-403, 2017

3 Ali MS, "Upper airway mucin gene expression : A review" 117 (117): 932-938, 2007

4 Matté A, "The novel role of peroxiredoxin-2 in red cell membrane protein homeostasis and senescence" 76 : 80-88, 2014

5 Yan F, "Reactive oxygen species regulate Pseudomonas aeruginosa lipopolysaccharideinduced MUC5AC mucin expression via PKC-NADPH oxidaseROS-TGF-alpha signaling pathways in human airway epithelial cells" 366 (366): 513-519, 2008

6 Rada B, "Reactive oxygen species mediate inflammatory cytokine release and EGFR-dependent mucin secretion in airway epithelial cells exposed to Pseudomonas pyocyanin" 4 (4): 158-171, 2011

7 Kim SK, "Protective effects of diphenyleneiodonium, an NADPH oxidase inhibitor, on lipopolysaccharide-induced acute lung injury" 46 (46): 153-162, 2019

8 Yang D, "Peroxiredoxin 6 suppresses Muc5ac overproduction in LPS-induced airway inflammation through H2O2-EGFR-MAPK signaling pathway" 236 : 84-90, 2017

9 Hewson CA, "PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms" 344 (344): 683-695, 2004

10 Wiegman CH, "Oxidative stress-induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease" 136 (136): 769-780, 2015

11 Ishii T, "Novel roles of peroxiredoxins in inflammation, cancer and innate immunity" 50 (50): 91-105, 2012

12 Fischer BM, "Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species" 26 (26): 447-452, 2002

13 Ridley C, "Mucins : The frontline defence of the lung" 46 (46): 1099-1106, 2018

14 Roy MG, "Muc5b is required for airway defence" 505 (505): 412-416, 2014

15 Hsu HY, "Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1gene expression" 277 (277): 22131-22139, 2002

16 Smirnova MG, "LPS up-regulates mucin and cytokine mRNA expression and stimulates mucin and cytokine secretion in goblet cells" 221 (221): 42-49, 2003

17 Lee TH, "Inhibition of peroxiredoxin 2 suppresses Wnt/β-catenin signaling in gastric cancer" 512 (512): 250-255, 2019

18 Murphy MP, "How mitochondria produce reactive oxygen species" 417 (417): 1-13, 2009

19 Lim SK, "Formaldehyde induces apoptosis through decreased Prx 2 via p38 MAPK in lung epithelial cells" 271 (271): 100-106, 2010

20 Moon EY, "Differential role of peroxiredoxin II(PrxII)on the expression of toll-like receptor 4(TLR4)and B-cell activating factor(BAFF)in ovalbumin(OVA)-induced mouse asthma" 8 (8): 935-944, 2008

21 Ishida YI, "Differential oxidation processes of peroxiredoxin 2 dependent on the reaction with several peroxides in human red blood cells" 518 (518): 685-690, 2019

22 Jin MH, "Characterization of neural cell types expressing peroxiredoxins in mouse brain" 381 (381): 252-257, 2005

23 Petrônio MS, "Apocynin : Chemical and biophysical properties of a NADPH oxidase inhibitor" 18 (18): 2821-2839, 2013

24 Na HG, "Allethrin and prallethrin stimulates MUC5AC expression through oxidative stress in human airway epithelial cells" 503 (503): 316-322, 2018

25 Bonser LR, "Airway mucus and asthma : The role of MUC5AC and MUC5B" 6 (6): 112-, 2017

26 Lachowicz-Scroggins ME, "Abnormalities in MUC5AC and MUC5B protein in airway mucus in asthma" 194 (194): 1296-1299, 2016