Airborne particulate matter increases MUC5AC expression by downregulating Claudin-1 expression in human airway cells
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
CLB2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates CLB2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB2.0. While the overexpression of claudin-1 decreased CLB2.0- induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. CLB2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetylcysteine inhibited CLB2.0-induced IL-6 secretion, thereby decreasing the CLB2.0-induced MUC5AC expression, whereas CLB2.0-induced MUC1 expression increased. CLB2.0 activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated the claudin-1 and MUC1 expressions, whereas it dramatically increased CLB2.0-induced MUC5AC expression. These findings suggest that CLB2.0-induced ERK1/2 activation acts as a switch for regulating inflammatory conditions though a ROS-dependent pathway. Our data also suggest that secreted IL-6 regulates CLB2.0-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway.
Abstract
CLB2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates CLB2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB2.0. While the overexpression of claudin-1 decreased CLB2.0- induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. CLB2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetylcysteine inhibited CLB2.0-induced IL-6 secretion, thereby decreasing the CLB2.0-induced MUC5AC expression, whereas CLB2.0-induced MUC1 expression increased. CLB2.0 activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated the claudin-1 and MUC1 expressions, whereas it dramatically increased CLB2.0-induced MUC5AC expression. These findings suggest that CLB2.0-induced ERK1/2 activation acts as a switch for regulating inflammatory conditions though a ROS-dependent pathway. Our data also suggest that secreted IL-6 regulates CLB2.0-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway.
참고문헌 (29)
- 송경섭, "KATP Channel Controls LPS-Induced MUC5AC Overexpression In Vivo", 조직공학과 재생의학, 8(2), pp.248~252 (2011), 한국조직공학과 재생의학회
- Valavanidis A, "Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms", J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 26, pp.339~362 (2008)
- Yu H, "Regulation of particulate matter-induced mucin secretion by transient receptor potential vanilloid 1 receptors", Inflammation, 35, pp.1851~1859 (2012)
- Song KS, "cAMP-responding element-binding protein and c-Ets1 interact in the regulation of ATP-dependent MUC5AC gene expression", J Biol Chem, 283, pp.26869~26878 (2008)
- Rose MC, "Respiratory tract mucin genes and mucin glycoproteins in health and disease", Physiol Rev, 86, pp.245~278 (2006)
- Rose MC, "Airway mucus obstruction: mucin glycoproteins, MUC gene regulation and goblet cell hyperplasia", Am J Respir Cell Mol Biol, 25, pp.533~537 (2001)
- Yoshida Y, "Tight junction transmembrane protein Claudin subtype expression and distribution in human corneal and conjunctival epithelium", Invest Ophthalmol Vis Sci, 50, pp.2103~2108 (2009)
- Escudero-Esparza A, "The Claudin family and its role in cancer and metastasis", Front Biosci (Landmark Ed), 16, pp.1069~1083 (2011)
- Furuse M, "Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from Claudin-1-deficient mice", J Cell Biol, 156, pp.1099~1111 (2002)
- Morin PJ, "Claudin proteins in human cancer: promising new targets for diagnosis and therapy", Cancer Res, 65, pp.9603~9606 (2005)
- Coyne CB, "Role of Claudin interactions in airway tight junctional permeability", Am J Physiol Lung Cell Mol Physiol, 285, pp.L1166~L1178 (2003)
- Becker S, "Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: further mechanistic studies", Toxicol Appl Pharmacol, 207, pp.269~275 (2005)
- Zhao Y, "Regulation of COX-2 expression and IL-6 release by particulate matter in airway epithelial cells", Am J Respir Cell Mol Biol, 40, pp.19~30 (2009)
- Wang T, "Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation", Part Fibre Toxicol, 9, pp.35~ (2012)
- Iwanaga K, "Urban particulate matter induces pro-remodeling factors by airway epithelial cells from healthy and asthmatic children", Inhal Toxicol, 25, pp.653~660 (2013)
- Val S, "Fine PM induce airway MUC5AC expression through the autocrine effect of amphiregulin", Arch Toxicol, 86, pp.1851~1859 (2012)
- Choi S, "TNF- is a key regulator of MUC1, an anti-inflammatory molecule, during airway Pseudomonas aeruginosa infection", Am J Respir Cell Mol Biol, 44, pp.255~260 (2011)
- Kim KC, "Role of epithelial mucins during airway infection", Pulm Pharmacol Ther, 25, pp.415~419 (2012)
- Kato K, "Membrane- Tethered MUC1 Mucin Counter-Regulates the Phagocytic Activity of Macrophages", Am J Respir Cell Mol Biol, 54, pp.515~523 (2016)
- Choi IW, "Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein", Sci Rep, 6, pp.27054~ (2016)
- Rogers DF, "Physiology of airway mucus secretion and pathophysiology of hypersecretion", Respir Care, 52, pp.1134~1146 (2007)
- Groneberg DA, "Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung", Respir Med, 96, pp.81~86 (2002)
- Johnson L, "MUC5AC and inflammatory mediators associated with respiratory outcomes in the British 1946 birth cohort", Respirology, 18, pp.1003~1010 (1946)
- Jeong JY, "IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction via PLCβ3 during Airway Inflammation", Mediators Inflamm, 2016, pp.7984853~ (2016)
- Wang T, "Particulate matter disrupts human lung endothelial barrier integrity via ROS- and p38 MAPK-dependent pathways", Am J Respir Cell Mol Biol, 42, pp.442~449 (2010)
- Caraballo JC, "Ambient particulate matter affects occludin distribution and increases alveolar transepithelial electrical conductance", Respirology, 16, pp.340~349 (2011)
- Gao SP, "Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas", J Clin Invest, 117, pp.3846~3856 (2007)
- Ting JP, "The NLR gene family: a standard nomenclature", Immunity, 28, pp.285~287 (2008)
- Øvrevik J, "Activation of proinflammatory responses in cells of the airway mucosa by particulate matter: Oxidant- and non-oxidant-mediated triggering mechanisms", Biomolecules, 5, pp.1399~1440 (2015)