Afzelin suppresses proinflammatory responses in particulate matter-exposed human keratinocytes

Kim,Ju   Hee; Kim,Minjeong; Kim,Jae  Min; Lee,Mi‑Kyung; Seo,Seong   Jun; Park,Kui   Young

doi:10.3892/ijmm.2019.4162

Afzelin suppresses proinflammatory responses in particulate matter-exposed human keratinocytes

Authors:
- Ju Hee Kim
- Minjeong Kim
- Jae Min Kim
- Mi‑Kyung Lee
- Seong Jun Seo
- Kui Young Park
View Affiliations

Affiliations: Department of Dermatology, Chung‑Ang University Hospital, Seoul 06973, Republic of Korea, Department of Laboratory Medicine, Chung‑Ang University Hospital, Seoul 06973, Republic of Korea
Published online on: April 11, 2019 https://doi.org/10.3892/ijmm.2019.4162
Pages: 2516-2522

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Particulate matter (PM), a widespread airborne contaminant, is a complex mixture of solid and liquid particles suspended in the air. Recent studies have demonstrated that PM induces oxidative stress and inflammatory reactions, and may cause certain skin diseases. Afzelin is a flavonoid isolated from Thesium chinense Turcz, which has anti‑inflammatory, anticancer and antibacterial properties. Therefore, the present study aimed to investigate if afzelin affected inflammatory responses in human keratinocytes exposed to PM. HaCaT cells were treated with PM (25 µg/cm2) in the presence or absence of afzelin (200 µM). Here, standard reference material 1649b was used as PM. Cell viability was assessed using the water‑soluble tetrazolium salt‑1 assay. The generation of reactive oxygen species (ROS) was measured using the dichloro‑dihydro‑fluorescein diacetate assay. Gene and protein expression were investigated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. Levels of secreted inflammatory cytokines were measured using ELISA. The results suggested that afzelin inhibited PM‑induced proinflammatory cytokine mRNA expression and protein secretion in HaCaT cells. In addition, afzelin suppressed PM‑induced intracellular ROS generation, and p38 mitogen‑activated protein kinase and transcription factor activator protein‑1 component c‑Fos and c‑Jun activation. The results indicated that afzelin exerts anti‑inflammatory and antioxidant effects in PM‑exposed HaCaT. Afzelin may have potential for preventing PM‑induced inflammatory skin diseases.

View Figures

View References

1	Kim KE, Cho D and Park HJ: Air pollution and skin diseases: Adverse effects of airborne particulate matter on various skin diseases. Life Sci. 152:126–134. 2016. View Article : Google Scholar : PubMed/NCBI
2	Mancebo SE and Wang SQ: Recognizing the impact of ambient air pollution on skin health. J Eur Acad Dermatol Venereol. 29:2326–2332. 2015. View Article : Google Scholar : PubMed/NCBI
3	Magnani ND, Muresan XM, Belmonte G, Cervellati F, Sticozzi C, Pecorelli A, Miracco C, Marchini T, Evelson P and Valacchi G: Skin damage mechanisms related to airborne particulate matter exposure. Toxicol Sci. 149:227–236. 2016. View Article : Google Scholar
4	Kampa M and Castanas E: Human health effects of air pollution. Environ Pollut. 151:362–367. 2008. View Article : Google Scholar
5	Du Y, Xu X, Chu M, Guo Y and Wang J: Air particulate matter and cardiovascular disease: The epidemiological, biomedical and clinical evidence. J Thorac Dis. 8:E8–E19. 2016.PubMed/NCBI
6	Guarnieri M and Balmes JR: Outdoor air pollution and asthma. Lancet. 383:1581–1592. 2014. View Article : Google Scholar : PubMed/NCBI
7	Bickers DR and Athar M: Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol. 126:2565–2575. 2006. View Article : Google Scholar : PubMed/NCBI
8	Segre JA: Epidermal barrier formation and recovery in skin disorders. J Clin Invest. 116:1150–1158. 2006. View Article : Google Scholar : PubMed/NCBI
9	Pan TL, Wang PW, Aljuffali IA, Huang CT, Lee CW and Fang JY: The impact of urban particulate pollution on skin barrier function and the subsequent drug absorption. J Dermatol Sci. 78:51–60. 2015. View Article : Google Scholar : PubMed/NCBI
10	Kim J, Kim EH, Oh I, Jung K, Han Y, Cheong HK and Ahn K: Symptoms of atopic dermatitis are influenced by outdoor air pollution. J Allergy Clin Immunol. 132:495–498.e1. 2013. View Article : Google Scholar : PubMed/NCBI
11	Vierkotter A, Schikowski T, Ranft U, Sugiri D, Matsui M, Krämer U and Krutmann J: Airborne particle exposure and extrinsic skin aging. J Invest Dermatol. 130:2719–2726. 2010. View Article : Google Scholar : PubMed/NCBI
12	Jin SP, Li Z, Choi EK, Lee S, Kim YK, Seo EY, Chung JH and Cho S: Urban particulate matter in air pollution penetrates into the barrier-disrupted skin and produces ROS-dependent cutaneous inflammatory response in vivo. J Dermatol Sci. S0923–1811. 30202–30210. 2018.PubMed/NCBI
13	Lee CW, Lin ZC, Hu SC, Chiang YC, Hsu LF, Lin YC, Lee IT, Tsai MH and Fang JY: Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction. Sci Rep. 6:279952016. View Article : Google Scholar : PubMed/NCBI
14	Krutmann J, Liu W, Li L, Pan X, Crawford M, Sore G and Seite S: Pollution and skin: From epidemiological and mechanistic studies to clinical implications. J Dermatol Sci. 76:163–168. 2014. View Article : Google Scholar : PubMed/NCBI
15	Lee CW, Lin ZC, Hsu LF, Fang JY, Chiang YC, Tsai MH, Lee MH, Li SY, Hu SC, Lee IT and Yen FL: Eupafolin ameliorates COX-2 expression and PGE2 production in particulate pollutants-exposed human keratinocytes through ROS/MAPKs pathways. J Ethnopharmacol. 189:300–309. 2016. View Article : Google Scholar : PubMed/NCBI
16	McCubrey JA, LaHair MM and Franklin RA: Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Antioxid Redox Signal. 8:1775–1789. 2006. View Article : Google Scholar : PubMed/NCBI
17	Parveen Z, Deng Y, Saeed MK, Dai R, Ahamad W and Yu YH: Antiinflammatory and analgesic activities of Thesium chinense Turcz extracts and its major flavonoids, kaempferol and kaemp-ferol-3-O-glucoside. Yakugaku Zasshi. 127:1275–1279. 2007. View Article : Google Scholar : PubMed/NCBI
18	Lee IK, Kim KH, Choi SU, Lee JH and Lee KR: Phytochemical constituents of Thesium chinense TURCZ and their cytotoxic activities in vitro. Natural Product Sciences. 15:246–249. 2009.
19	Kim SK, Kim HJ, Choi SE, Park KH, Choi HK and Lee MW: Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E2 (COX-2) production of flavonoids from seeds of prunus tomentosa thunberg. Arch Pharm Res. 31:424–428. 2008. View Article : Google Scholar : PubMed/NCBI
20	Diantini A, Subarnas A, Lestari K, Halimah E, Susilawati Y, Supriyatna, Julaeha E, Achmad TH, Suradji EW, Yamazaki C, et al: Kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii korth inhibits MCF-7 breast cancer cell proliferation through activation of the caspase cascade pathway. Oncol Lett. 3:1069–1072. 2012. View Article : Google Scholar : PubMed/NCBI
21	Lee SY, So YJ, Shin MS, Cho JY and Lee J: Antibacterial effects of afzelin isolated from Cornus macrophylla on Pseudomonas aeruginosa, a leading cause of illness in immunocompromised individuals. Molecules. 19:3173–3180. 2014. View Article : Google Scholar : PubMed/NCBI
22	Shin SW, Jung E, Kim S, Kim JH, Kim EG, Lee J and Park D: Antagonizing effects and mechanisms of afzelin against UVB-induced cell damage. PLoS One. 8:e619712013. View Article : Google Scholar : PubMed/NCBI
23	Jung E, Kim JH, Kim MO, Jang S, Kang M, Oh SW, Nho YH, Kang SH, Kim MH, Park SH and Lee J: Afzelin positively regulates melanogenesis through the p38 MAPK pathway. Chem Biol Interact. 254:167–172. 2016. View Article : Google Scholar : PubMed/NCBI
24	Eruslanov E and Kusmartsev S: Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol Biol. 594:57–72. 2010. View Article : Google Scholar : PubMed/NCBI
25	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
26	Drakaki E, Dessinioti C and Antoniou CV: Air pollution and the skin. Front Environ Sci. 2:112014. View Article : Google Scholar
27	Tekpli X, Holme JA, Sergent O and Lagadic-Gossmann D: Importance of plasma membrane dynamics in chemical-induced carcinogenesis. Recent Pat Anticancer Drug Discov. 6:347–353. 2011. View Article : Google Scholar : PubMed/NCBI
28	Li N, Xia T and Nel AE: The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med. 44:1689–1699. 2008. View Article : Google Scholar : PubMed/NCBI
29	Wang J, Huang J, Wang L, Chen C, Yang D, Jin M, Bai C and Song Y: Urban particulate matter triggers lung inflammation via the ROS-MAPK-NF-κB signaling pathway. J Thorac Dis. 9:4398–4412. 2017. View Article : Google Scholar : PubMed/NCBI
30	Lobo V, Patil A, Phatak A and Chandra N: Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev. 4:118–126. 2010. View Article : Google Scholar : PubMed/NCBI
31	Ushio H, Nohara K and Fujimaki H: Effect of environmental pollutants on the production of pro-inflammatory cytokines by normal human dermal keratinocytes. Toxicol Lett. 105:17–24. 1999. View Article : Google Scholar : PubMed/NCBI
32	Choi H, Shin DW, Kim W, Doh SJ, Lee SH and Noh M: Asian dust storm particles induce a broad toxicological transcriptional program in human epidermal keratinocytes. Toxicol Lett. 200:92–99. 2011. View Article : Google Scholar
33	Li Q, Kang Z, Jiang S, Zhao J, Yan S, Xu F and Xu J: Effects of ambient fine particles PM_2.5 on human HaCaT cells. Int J Environ Res Public Health. 14:E722017. View Article : Google Scholar