Skip to main content

Advertisement

Log in

Para-phenylenediamine, an oxidative hair dye ingredient, increases thymic stromal lymphopoietin and proinflammatory cytokines causing acute dermatitis

  • Original Article
  • Published:
Toxicological Research Aims and scope Submit manuscript

Abstract

Due to high consumption of cosmetics in modern society, people are always exposed to the risk of skin damage and complications. Para-phenylenediamine (P-PD), an ingredient of hair dye, has been reported to cause allergic contact dermatitis. However, the mechanism has not been well elucidated. Here, we identify that P-PD causes dermatitis by increasing thymic stromal lymphopoietin (TSLP) and inflammatory cytokines. Topical application of P-PD to mouse ear skin in consecutive 5 days resulted in dermatitis symptoms and increased ear thickness. TSLP production in skin was upregulated by P-PD treatment alone. In addition, P-PD-induced TSLP production was potentiated by MC903, which is an in vivo TSLP inducer. P-PD increased TSLP production in keratinocytes (KCMH-1 cells and phorbol 12-myristate 13-acetate-stimulated PAM212 cells). The production of proinflammatory cytokines such as IL-1β, IL-6, IFN-γ, and CCL2, was upregulated by P-PD treatment together with MC903. The results show that repeated exposure to P-PD causes acute contact dermatitis mediated by increasing the expression of TSLP and proinflammatory cytokines.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chen X, Sullivan DA, Sullivan AG, Kam WR, Liu Y (2018) Toxicity of cosmetic preservatives on human ocular surface and adnexal cells. Exp Eye Res 170:188–197. https://doi.org/10.1016/j.exer.2018.02.020

    Article  CAS  PubMed  Google Scholar 

  2. Nohynek GJ, Fautz R, Benech-Kieffer F, Toutain H (2004) Toxicity and human health risk of hair dyes. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 42:517–543. https://doi.org/10.1016/j.fct.2003.11.003

    Article  CAS  Google Scholar 

  3. McFadden JP, White IR, Frosch PJ, Sosted H, Johansen JD, Menne T (2007) Allergy to hair dye. BMJ 334:220. https://doi.org/10.1136/bmj.39042.643206.BE

    Article  PubMed  PubMed Central  Google Scholar 

  4. McFadden JP, Yeo L, White JL (2011) Clinical and experimental aspects of allergic contact dermatitis to para-phenylenediamine. Clin Dermatol 29:316–324. https://doi.org/10.1016/j.clindermatol.2010.11.011

    Article  PubMed  Google Scholar 

  5. Oakes T, Popple AL, Williams J, Best K, Heather JM, Ismail M, Maxwell G, Gellatly N, Dearman RJ, Kimber I, Chain B (2017) The T cell response to the contact sensitizer paraphenylenediamine is characterized by a polyclonal diverse repertoire of antigen-specific receptors. Front Immunol 8:162. https://doi.org/10.3389/fimmu.2017.00162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Vogel TA, Coenraads PJ, Bijkersma LM, Vermeulen KM, Schuttelaar ML (2015) p-Phenylenediamine exposure in real life—a case–control study on sensitization rate, mode and elicitation reactions in the northern Netherlands. Contact Dermat 72:355–361. https://doi.org/10.1111/cod.12354

    Article  CAS  Google Scholar 

  7. Basketter DA, Goodwin BF (1988) Investigation of the prohapten concept. Cross reactions between 1,4-substituted benzene derivatives in the guinea pig. Contact Dermat 19:248–253

    Article  CAS  Google Scholar 

  8. Nacaroglu HT, Yavuz S, Basman E, Bahceci S, Tasdemir M, Yigit O, Can D (2015) The clinical spectrum of reactions developed based on paraphenylenediamine hypersensitivity two pediatric cases. Postepy dermatologii i alergologii 32:393–395. https://doi.org/10.5114/pdia.2015.52738

    Article  PubMed  PubMed Central  Google Scholar 

  9. Mukkanna KS, Stone NM, Ingram JR (2017) Para-phenylenediamine allergy: current perspectives on diagnosis and management. J Asthma Allergy 10:9–15. https://doi.org/10.2147/jaa.S90265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Thyssen JP, White JM (2008) Epidemiological data on consumer allergy to p-phenylenediamine. Contact Dermat 59:327–343. https://doi.org/10.1111/j.1600-0536.2008.01427.x

    Article  CAS  Google Scholar 

  11. Sharma VK, Chakrabarti A (1998) Common contact sensitizers in Chandigarh, India. A study of 200 patients with the European standard series. Contact Dermat 38:127–131

    Article  CAS  Google Scholar 

  12. Ziegler SF (2012) Thymic stromal lymphopoietin and allergic disease. J Allergy Clin Immunol 130:845–852. https://doi.org/10.1016/j.jaci.2012.07.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Leyva-Castillo JM, Hener P, Michea P, Karasuyama H, Chan S, Soumelis V, Li M (2013) Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade. Nat Commun 4:2847. https://doi.org/10.1038/ncomms3847

    Article  CAS  PubMed  Google Scholar 

  14. Wong CK, Hu S, Cheung PF, Lam CW (2010) Thymic stromal lymphopoietin induces chemotactic and prosurvival effects in eosinophils: implications in allergic inflammation. Am J Respir Cell Mol Biol 43:305–315. https://doi.org/10.1165/rcmb.2009-0168OC

    Article  CAS  PubMed  Google Scholar 

  15. Segawa R, Yamashita S, Mizuno N, Shiraki M, Hatayama T, Satou N, Hiratsuka M, Hide M, Hirasawa N (2014) Identification of a cell line producing high levels of TSLP: advantages for screening of anti-allergic drugs. J Immunol Methods 402:9–14. https://doi.org/10.1016/j.jim.2013.10.012

    Article  CAS  PubMed  Google Scholar 

  16. Yuspa SH, Hawley-Nelson P, Koehler B, Stanley JR (1980) A survey of transformation markers in differentiating epidermal cell lines in culture. Cancer Res 40:4694–4703

    CAS  PubMed  Google Scholar 

  17. Yang G, Lee HE, Lim KM, Choi YK, Kim KB, Lee BM, Lee JY (2018) Potentiation of skin TSLP production by a cosmetic colorant leads to aggravation of dermatitis symptoms. Chem Biol Interact 284:41–47. https://doi.org/10.1016/j.cbi.2018.02.020

    Article  CAS  PubMed  Google Scholar 

  18. Lee HE, Yang G, Han SH, Lee JH, An TJ, Jang JK, Lee JY (2018) Anti-obesity potential of Glycyrrhiza uralensis and licochalcone A through induction of adipocyte browning. Biochem Biophys Res Commun 503:2117–2123. https://doi.org/10.1016/j.bbrc.2018.07.168

    Article  CAS  PubMed  Google Scholar 

  19. Yang G, Koo JE, Lee HE, Shin SW, Um SH, Lee JY (2019) Immunostimulatory activity of Y-shaped DNA nanostructures mediated through the activation of TLR9. Biomed Pharmacother 112:108657. https://doi.org/10.1016/j.biopha.2019.108657

    Article  CAS  PubMed  Google Scholar 

  20. Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P (2006) Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc Natl Acad Sci USA 103:11736–11741. https://doi.org/10.1073/pnas.0604575103

    Article  CAS  PubMed  Google Scholar 

  21. Jang HY, Koo JH, Lee SM, Park BH (2018) Atopic dermatitis-like skin lesions are suppressed in fat-1 transgenic mice through the inhibition of inflammasomes. Exp Mol Med 50:73. https://doi.org/10.1038/s12276-018-0104-3

    Article  CAS  Google Scholar 

  22. Dai J, Choo MK, Park JM, Fisher DE (2017) Topical ROR inverse agonists suppress inflammation in mouse models of atopic dermatitis and acute irritant dermatitis. J Investig Dermatol 137:2523–2531. https://doi.org/10.1016/j.jid.2017.07.819

    Article  CAS  PubMed  Google Scholar 

  23. Lee HC, Ziegler SF (2007) Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB. Proc Natl Acad Sci USA 104:914–919. https://doi.org/10.1073/pnas.0607305104

    Article  CAS  PubMed  Google Scholar 

  24. Divekar R, Kita H (2015) Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation. Curr Opin Allergy Clin Immunol 15:98–103. https://doi.org/10.1097/aci.0000000000000133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Klonowska J, Glen J, Nowicki RJ, Trzeciak M (2018) New cytokines in the pathogenesis of atopic dermatitis-new therapeutic targets. Int J Mol Sci. https://doi.org/10.3390/ijms19103086

    Article  PubMed  PubMed Central  Google Scholar 

  26. Reena K, Ng KY, Koh RY, Gnanajothy P, Chye SM (2017) Para-phenylenediamine induces apoptosis through activation of reactive oxygen species-mediated mitochondrial pathway, and inhibition of the NF-kappaB, mTOR, and Wnt pathways in human urothelial cells. Environ Toxicol 32:265–277. https://doi.org/10.1002/tox.22233

    Article  CAS  PubMed  Google Scholar 

  27. Zaid Y, Marhoume F, Senhaji N, Kojok K, Boufous H, Naya A, Oudghiri M, Darif Y, Habti N, Zouine S, Mohamed F, Chait A, Bagri A (2016) Paraphenylene diamine exacerbates platelet aggregation and thrombus formation in response to a low dose of collagen. J Toxicol Sci 41:123–128. https://doi.org/10.2131/jts.41.123

    Article  CAS  PubMed  Google Scholar 

  28. Oyoshi MK, He R, Kumar L, Yoon J, Geha RS (2009) Cellular and molecular mechanisms in atopic dermatitis. Adv Immunol 102:135–226. https://doi.org/10.1016/s0065-2776(09)01203-6

    Article  CAS  PubMed  Google Scholar 

  29. Noske K (2018) Secreted immunoregulatory proteins in the skin. J Dermatol Sci 89:3–10. https://doi.org/10.1016/j.jdermsci.2017.10.008

    Article  CAS  PubMed  Google Scholar 

  30. Johnson-Huang LM, Suarez-Farinas M, Pierson KC, Fuentes-Duculan J, Cueto I, Lentini T, Sullivan-Whalen M, Gilleaudeau P, Krueger JG, Haider AS, Lowes MA (2012) A single intradermal injection of IFN-gamma induces an inflammatory state in both non-lesional psoriatic and healthy skin. J Investig Dermatol 132:1177–1187. https://doi.org/10.1038/jid.2011.458

    Article  CAS  PubMed  Google Scholar 

  31. Giustizieri ML, Mascia F, Frezzolini A, De Pita O, Chinni LM, Giannetti A, Girolomoni G, Pastore S (2001) Keratinocytes from patients with atopic dermatitis and psoriasis show a distinct chemokine production profile in response to T cell-derived cytokines. J Allergy Clin Immunol 107:871–877. https://doi.org/10.1067/mai.2001.114707

    Article  CAS  PubMed  Google Scholar 

  32. Kasi RA, Moi CS, Kien YW, Yian KR, Chin NW, Yen NK, Ponnudurai G, Fong SH (2015) Para-phenylenediamine-induces apoptosis via a pathway dependent on PTK-Ras-Raf-JNK activation but independent of the PI3K/Akt pathway in NRK-52E cells. Mol Med Rep 11:2262–2268. https://doi.org/10.3892/mmr.2014.2979

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants (18172MFDS231 and 19172MFDS221) from the Ministry of Food and Drug Safety, Korea in 2018 and 2019.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joo Young Lee.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, J.K., Lee, H.E., Yang, G. et al. Para-phenylenediamine, an oxidative hair dye ingredient, increases thymic stromal lymphopoietin and proinflammatory cytokines causing acute dermatitis. Toxicol Res. 36, 329–336 (2020). https://doi.org/10.1007/s43188-020-00041-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43188-020-00041-6

Keywords

Navigation