Abstract
Oxidative stress (OS) is common in inflammatory conditions and may be important in atopic dermatitis (AD) etiology. The aim of this project was to study the involvement of oxidation in FSL-1 (deacylated lipoprotein)-triggered signaling pathways leading to AD-typical cytokine expression in HaCaT keratinocytes. HaCaT keratinocytes, pretreated with the inhibitor to OS N-acetylcysteine (NAC), were exposed to FSL-1, a stimulator of AD-related cytokines. Cytokines expression was studied by real time polymerase chain reaction (PCR); nuclear factor-kappa B (NF-κB) and p38 mitogen activated protein kinase (MAPK) activities were studied by western blotting; and the oxidative state of cells was determined by the dichlorofluorescein (DCF) assay. We found that endogenous OS in keratinocytes appeared 4 h after FSL-1 administration. OS activated NF-κB, but not p38 MAPK, and the inhibition of OS reduced FSL-1 induced interleukin (IL) 33, thymic stromal lymphopoietin (TSLP) and TNFα mRNA expression. We conclude that FSL-1 triggers an OS reaction in HaCaT keratinocytes, which is probably a secondary event affecting the expression of specific AD typical cytokines, possibly through the NF-κB pathways. This role of OS in the inflammatory response in AD is worth further investigating.
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References
Boguniewicz M, Leung DY (2010) Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol 125:4–13
Carmi-Levy I, Homey B, Soumelis V (2011) A modular view of cytokines networks in atopic dermatitis. Clin Rev Allerg Immunol 41:245–253
Gochman E, Mahajna J, Reznick AZ (2011) NF-κB activation by peroxynitrite through IκBα-dependent phosphorylation versus nitration in colon cancer cells. Anticancer Res 31:1607–1617
Guttman-Yassky E, Dhingra N, Leung DYM (2013) New era of biologic therapeutics in atopic dermatitis. Expert Opin 13:549–561
Hvid M, Vestergaad C, Kemp K, Chrisensen GB, Deleuran B, Deleuran M (2011) IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction. J Investig Dermatol 121:150–157
Kaisari S, Rom O, Aizenbud D, Reznick AZ (2013) The involvement of NF-κB and muscle specific E3 ubiquitin ligase MuRF1 in cigarette smoke induced catabolism in C2 myotubes. Adv Exp Med Biol 788:7–17
Kim D, Byamba D, Wu WH, Kim T, Lee M (2011) Different characteristics of reactive oxygen species production by human keratinocytes cell line cells in response to allergens and irritants. Exp Dermatol 21:99–103
Kumar S, Boehm J, Lee JC (2003) P38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nature Rev 2:717–726
Lenung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA (2004) New insights into atopic dermatitis. J Clin Ivest 113:651–657
Loukili N, Rosenblatt-Velin N, Rolli J, Levrand S, Feihl F, Waeber B, Pacher P, Liaudet L (2010) Oxidants positively or negatively regulate nuclear factor κB in a context-dependent manner. J Biol Chem 285:15746–15752
Moon P, Kim H (2011) Thymic stromal lymphopoietin is expressed and produced by caspase-1/NF-κB in mast cells. Cytokine 54:239–243
Morishita R, Tomita N, Kaneda Y, Ogihara T (2004) Prevention and regression of atopic dermatitis by ointment containing NF-κB decoy oligodeoxynucleotides in NC/Nga atopic mouse model. Curr Opin Pharmacol 4:139–146
Niwa Y, Sumi H, Kawahira K, Terashima T, Nakamura T, Akamatsu H (2003) Protein oxidative damage to the stratum corneum: evidence for the link between environmental oxidation and changing prevalence and nature of atopic dermatitis in Japan. Br J Dermatol 149:248–254
Novak N, Simon D (2011) Atopic dermatitis – from new pathophysiologic insights to individualized therapy. Allergy 66:830–839
Patrizi A, Pileri A, Bellini F, Raone B, Neri I, Ricci P (2011) Atopic dermatitis and the atopic march: what is new? J Allergy (Cairo). doi:10.1155/2011/279425
Perkins ND (2006) Post-translational modifications regulating the activity and function of the nuclear factor B pathway. Oncogene 25:6717–6730
Peus D, Vasa RA, Beyerle A, Meves A, Krautmacher C, Pittelkow M (1999) UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes. J Investig Dermatol 112:751–756
Pushparaj PN, Tay H, H’ng S, Pitman N, Xu D, McKenzie A, Liew FY, Melendez AJ (2009) The cytokine interleukin-33 mediates anaphylactic shock. Proc Natl Acad Sci U S A 104:9773–9778
Terui T (2009) Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment: overview of the pathophysiology of atopic dermatitis. J Pharmacol Sci 110:232–236
Tsukahara H, Shibata R, Ohta N, Sato S, Hiraoka M, Ito S, Noiri E, Mayumi M (2003) High levels of urinary pentosidine, an advanced glycation end product, in children with acute exacerbation of atopic dermatitis: relationship with oxidative stress. Metab Clin Exp 52:1601–1605
Tuan Vu A, Baba T, Chen X, Le Anh T, Kinoshita H, Xie Y, Kamijo S, Hiramatsu K, Ikeda S, Ogawa H, Okumura K, Takai T (2010) Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2-Toll-like receptor 6 pathway. J Allergy Clin Immunol 126:985–993
Valencia A, Kochevar IE (2008) Nox1-based NADPH oxidase is the major source of UVA-induced reactive oxygen species in human keratinocytes. J Investig Dermatol 128:214–222
Zhaoa J, Benakanakerea MR, Hosurb KB, Galiciaa JC, Martinc M, Kinane DF (2010) Mammalian target of rapamycin (mTOR) regulates TLR3 induced cytokines in human oral keratinocytes. Mol Immunol 48:294–304
Acknowledgments
This work was supported by Rappaport Institute and by MIGAL – Galilee Research Institute.
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The authors declare no conflicts of interest in relation to this manuscript.
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Koren Carmi, I., Haj, R., Yehuda, H., Tamir, S., Reznick, A.Z. (2014). The Role of Oxidation in FSL-1 Induced Signaling Pathways of an Atopic Dermatitis Model in HaCaT Keratinocytes. In: Pokorski, M. (eds) Environmental Biomedicine. Advances in Experimental Medicine and Biology(), vol 849. Springer, Cham. https://doi.org/10.1007/5584_2014_98
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DOI: https://doi.org/10.1007/5584_2014_98
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