Background/Aims: Airborne particulate matter with a diameter of < 10 µm (PM10) causes oxidative damage, inflammation, and premature skin aging. In this study, we evaluated whether polyphenolic antioxidants attenuate the inflammatory responses of PM10-exposed keratinocytes. Methods: Primary human epidermal keratinocytes were exposed in vitro to PM10 in the absence or presence of punicalagin and (–)-epigallocatechin-3-gallate (EGCG), which are the major polyphenolic antioxidants found in pomegranate and green tea, respectively. Assays were performed to determine cell viability, production of reactive oxygen species (ROS), and expression of NADPH oxidases (NOX), proinflammatory cytokines, and matrix metalloproteinase (MMP)-1. Results: PM10 decreased cell viability and increased ROS production in a dose-dependent manner. It also increased the expression levels of NOX-1, NOX-2, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, and MMP-1. Punicalagin was not cytotoxic up to 300 μM, and (–)-EGCG was cytotoxic above 30 μM, respectively. Further, punicalagin (3–30 μM) and EGCG (3–10 μM) rescued the viability of PM10-exposed cells. They also attenuated ROS production and the expression of NOX-1, NOX-2, TNF-α, IL-1β, IL-6, IL-8, and MMP-1 stimulated by PM10. Conclusions: This study demonstrates that polyphenolic antioxidants, such as punicalagin and (–)-EGCG, rescue keratinocyte viability and attenuate the inflammatory responses of these cells due to airborne particles.

1.
Sacks JD, Stanek LW, Luben TJ, Johns DO, Buckley BJ, Brown JS, Ross M: Particulate matter-induced health effects: who is susceptible? Environ Health Perspect 2012; 119: 446–454.
2.
Anderson JO, Thundiyil JG, Stolbach A: Clearing the air: a review of the effects of particulate matter air pollution on human health. J Med Toxicol 2012; 8: 166–175.
3.
Donaldson K, Stone V, Clouter A, Renwick L, MacNee W: Ultrafine particles. Occup Environ Med 2001; 58: 211–216, 199.
4.
Li XY, Gilmour PS, Donaldson K, MacNee W: Free radical activity and pro-inflammatory effects of particulate air pollution (PM10) in vivo and in vitro. Thorax 1996; 51: 1216–1222.
5.
Guo L, Zhu N, Guo Z, Li GK, Chen C, Sang N, Yao QC: Particulate matter (PM10) exposure induces endothelial dysfunction and inflammation in rat brain. J Hazard Mater 2012; 213–214: 28–37.
6.
Hwang SH, Choi YH, Paik HJ, Wee WR, Kim MK, Kim DH: Potential importance of ozone in the association between outdoor air pollution and dry eye disease in South Korea. JAMA Ophthalmol 2016, Epub ahead of print.
7.
Kim KE, Cho D, Park HJ: Air pollution and skin diseases: adverse effects of airborne particulate matter on various skin diseases. Life Sci 2016; 152: 126–134.
8.
Vierkotter A, Schikowski T, Ranft U, Sugiri D, Matsui M, Kramer U, Krutmann J: Airborne particle exposure and extrinsic skin aging. J Invest Dermatol 2010; 130: 2719–2726.
9.
Donaldson K, Stone V: Current hypotheses on the mechanisms of toxicity of ultrafine particles. Ann Ist Super Sanita 2003; 39: 405–410.
10.
Ishii H, Fujii T, Hogg JC, Hayashi S, Mukae H, Vincent R, van Eeden SF: Contribution of IL-1 beta and TNF-alpha to the initiation of the peripheral lung response to atmospheric particulates (PM10). Am J Physiol Lung Cell Mol Physiol 2004; 287:L176–L183.
11.
Cho DY, Le W, Bravo DT, Hwang PH, Illek B, Fischer H, Nayak JV: Air pollutants cause release of hydrogen peroxide and interleukin-8 in a human primary nasal tissue culture model. Int Forum Allergy Rhinol 2014; 4: 966–971.
12.
Bedard K, Krause KH: The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007; 87: 245–313.
13.
Lassegue B, Griendling KK: NADPH oxidases: functions and pathologies in the vasculature. Arterioscler Thromb Vasc Biol 2010; 30: 653–661.
14.
Bengalli R, Molteni E, Longhin E, Refsnes M, Camatini M, Gualtieri M: Release of IL-1 beta triggered by Milan summer PM10: molecular pathways involved in the cytokine release. Biomed Res Int 2013; 2013: 158093.
15.
Fujii T, Hayashi S, Hogg JC, Mukae H, Suwa T, Goto Y, Vincent R, van Eeden SF: Interaction of alveolar macrophages and airway epithelial cells following exposure to particulate matter produces mediators that stimulate the bone marrow. Am J Respir Cell Mol Biol 2002; 27: 34–41.
16.
Morales-Barcenas R, Chirino YI, Sanchez-Perez Y, Osornio-Vargas AR, Melendez- Zajgla J, Rosas I, Garcia-Cuellar CM: Particulate matter (PM10) induces metalloprotease activity and invasion in airway epithelial cells. Toxicol Lett 2015; 237: 167–173.
17.
Lee SI, Kim HJ, Boo YC: Effect of green tea and (–)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells. Phytother Res 2008; 22: 669–674.
18.
Singh RP, Chidambara Murthy KN, Jayaprakasha GK: Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J Agric Food Chem 2002; 50: 81–86.
19.
Villarreal-Calderon R, Reed W, Palacios-Moreno J, Keefe S, Herritt L, Brooks D, Torres-Jardon R, Calderon-Garciduenas L: Urban air pollution produces up-regulation of myocardial inflammatory genes and dark chocolate provides cardioprotection. Exp Toxicol Pathol 2012; 64: 297–306.
20.
Park S, Seok JK, Kwak JY, Suh HJ, Kim YM, Boo YC: Anti-inflammatory effects of pomegranate peel extract in THP-1 cells exposed to particulate matter PM10. Evid Based Complement Alternat Med 2016; 2016: 6836080.
21.
Uysal U, Seremet S, Lamping JW, Adams JM, Liu DY, Swerdlow RH, Aires DJ: Consumption of polyphenol plants may slow aging and associated diseases. Curr Pharm Des 2013; 19: 6094–6111.
22.
Kalyanaraman B, Darley-Usmar V, Davies KJ, Dennery PA, Forman HJ, Grisham MB, Mann GE, Moore K, Roberts LJ 2nd, Ischiropoulos H: Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic Biol Med 2012; 52: 1–6.
23.
Kahari VM, Saarialho-Kere U: Matrix metalloproteinases in skin. Exp Dermatol 1997; 6: 199–213.
24.
Argyropoulos AJ, Robichaud P, Balimunkwe RM, Fisher GJ, Hammerberg C, Yan Y, Quan T: Alterations of dermal connective tissue collagen in diabetes: molecular basis of aged-appearing skin. PLoS One 2016; 11:e0153806.
25.
Pittayapruek P, Meephansan J, Prapapan O, Komine M, Ohtsuki M: Role of matrix metalloproteinases in photoaging and photocarcinogenesis. Int J Mol Sci 2016; 17:E868.
26.
Saputri RK, Setiawan B, Nugrahenny D, Kania N, Wahyuni ES, Widodo MA: The effects of Eucheuma cottonii on alveolar macrophages and malondialdehyde levels in bronchoalveolar lavage fluid in chronically particulate matter 10 coal dust-exposed rats. Iran J Basic Med Sci 2014; 17: 541–545.
27.
Wallach D, Kang TB, Kovalenko A: Concepts of tissue injury and cell death in inflammation: a historical perspective. Nat Rev Immunol 2014; 14: 51–59.
28.
Carreras A, Mateos-Martin ML, Velazquez-Palenzuela A, Brillas E, Sanchez-Tena S, Cascante M, Julia L, Torres JL: Punicalagin and catechins contain polyphenolic substructures that influence cell viability and can be monitored by radical chemosensors sensitive to electron transfer. J Agric Food Chem 2012; 60: 1659–1665.
29.
Joven J, Micol V, Segura-Carretero A, Alonso-Villaverde C, Menendez JA; Bioactive Food Components Platform: Polyphenols and the modulation of gene expression pathways: can we eat our way out of the danger of chronic disease? Crit Rev Food Sci Nutr 2014; 54: 985–1001.
30.
Park KH, Lee MW: Anti-oxidative, anti-inflammatory and whitening effects of phenolic compounds from Bambusae caulis in liquamen. Nat Prod Res 2012; 26: 1687–1691.
31.
Lee YM, Kim YK, Kim KH, Park SJ, Kim SJ, Chung JH: A novel role for the TRPV1 channel in UV-induced matrix metalloproteinase (MMP)-1 expression in HaCaT cells. J Cell Physiol 2009; 219: 766–775.
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