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Archives of Dermatological Research

, Volume 308, Issue 1, pp 49–54 | Cite as

Japanese Cedar (Cryptomeria japonica) pollen allergen induces elevation of intracellular calcium in human keratinocytes and impairs epidermal barrier function of human skin ex vivo

  • Junichi Kumamoto
  • Moe Tsutsumi
  • Makiko Goto
  • Masaharu Nagayama
  • Mitsuhiro DendaEmail author
Concise Communication

Abstract

Cry j1 is the major peptide allergen of Japanese cedar (Sugi), Cryptomeria japonica. Since some allergens disrupt epidermal permeability barrier homeostasis, we hypothesized that Cry j1 might have a similar effect. Intracellular calcium level in cultured human keratinocytes was measured with a ratiometric fluorescent probe, Fura-2 AM. Application of Cry j1 significantly increased the intracellular calcium level of keratinocytes, and this increase was inhibited by trypsin inhibitor or a protease-activated receptor 2 (PAR-2) antagonist. We found that Cry j1 itself did not show protease activity, but application of Cry j1 to cultured keratinocytes induced a rapid (within 30 s) and transient increase of protease activity in the medium. This transient increase was blocked by trypsin inhibitor or PAR-2 antagonist. The effect of Cry j1 on transepidermal water loss (TEWL) of cultured human skin was measured in the presence and absence of a trypsin inhibitor and PAR-2 antagonist. Cry j1 significantly impaired the barrier function of human skin ex vivo, and this action was blocked by co-application of trypsin inhibitor or PAR-2 antagonist. Our results suggested that interaction of Cry j1 with epidermal keratinocytes leads to the activation of PAR-2, which induces elevation of intracellular calcium and disruption of barrier function. Blocking the interaction of Cry j1 with epidermal keratinocytes might ameliorate allergic reaction and prevent disruption of epidermal permeability barrier homeostasis.

Keywords

Cry j1 Protease-activated receptor 2 PAR-2 Trypsin inhibitor FSLLRY-NH2 

Notes

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.

Supplementary material

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Supplementary material 1 (TIFF 4666 kb)
403_2015_1602_MOESM2_ESM.pdf (2.7 mb)
Supplementary material 2 (PDF 2797 kb)

References

  1. 1.
    Bando H, Sugiura H, Ohkusa Y, Akahane M, Sano T, Jojima N, Okabe N, Imamura T (2015) Association between first airborne cedar pollen level peak and pollinosis symptom onset: a web-based survey. Int J Environ Health Res 25:104–113PubMedCrossRefGoogle Scholar
  2. 2.
    Chen Y, Yang C, Wang ZJ (2011) Proteinase-activated receptor 2 sensitizes transient receptor potential vanilloid 1, transient receptor potential vanilloid 4, and transient receptor potential ankyrin 1 in paclitaxel-induced neuropathic pain. Neuroscience 193:440–451PubMedCrossRefGoogle Scholar
  3. 3.
    Demerjian M, Hachem JP, Tschachler E, Denecker G, Declercq W, Vandenabeele P, Mauro T, Hupe M, Crumrine D, Roelandt T, Houben E, Elias PM, Feingold KR (2008) Acute modulations in permeability barrier function regulate epidermal cornification: role of caspase-14 and the protease-activated receptor type 2. Am J Pathol 172:86–97PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Denda M, Fuziwara S, Inoue K (2003) Influx of calcium and chloride ions into epidermal keratinocytes regulates exocytosis of epidermal lamellar bodies and skin permeability barrier homeostasis. J Invest Dermatol 121:362–367PubMedCrossRefGoogle Scholar
  5. 5.
    Denda M, Kitamura K, Elias PM, Feingold KR (1997) Trans-4-(Aminomethyl) cyclohexane carboxylic acid (T-AMCHA), an anti-fibrinolytic agent, accelerates barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans. J Invest Dermatol 109:84–90PubMedCrossRefGoogle Scholar
  6. 6.
    Denda M, Sato J, Masuda Y, Tsuchiya T, Koyama J, Kuramoto M, Elias PM, Feingold KR (1998) Exposure to a dry environment enhances epidermal permeability barrier function. J Invest Dermatol 111:858–863PubMedCrossRefGoogle Scholar
  7. 7.
    Hanley K, Rassner U, Elias PM, Williams ML, Feingold KR (1996) Epidermal barrier ontogenesis: maturation in serum-free media and acceleration by glucocorticoids and thyroid hormone but not selected growth factors. J Invest Dermatol. 106:404–411PubMedCrossRefGoogle Scholar
  8. 8.
    Ibrahim AR, Kawamoto S, Aki T, Shimada Y, Rikimaru S, Onishi N, Babiker EE, Oiso I, Hashimoto K, Hayashi T, Ono K (2010) Molecular cloning and immunochemical characterization of a novel major Japanese cedar pollen allergen belonging to the aspartic protease family. Int Arch Allergy Immunol 152:207–218PubMedCrossRefGoogle Scholar
  9. 9.
    Jeong SK, Kim HJ, Youm JK, Ahn SK, Choi EH, Sohn MH, Kim KE, Hong JH, Shin DM, Lee SH (2008) Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery. J Invest Dermatol 128:1930–1939PubMedCrossRefGoogle Scholar
  10. 10.
    Mägert HJ, Drögemüller K, Raghunath M (2005) Serine proteinase inhibitors in the skin: role in homeostasis and disease. Curr Protein Pept Sci 6:241–254PubMedCrossRefGoogle Scholar
  11. 11.
    Patel KN, Liu Q, Meeker S, Undem BJ, Dong X (2011) Pirt, a TRPV1 modulator, is required for histamine-dependent and -independent itch. PLoS One 6:e20559PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Sheikh A, Panesar SS, Salvilla S, Dhami S (2009) Hay fever in adolescents and adults. Clin Evid (Online) 2 2009: 0509. Published online Nov 18, 2009Google Scholar
  13. 13.
    Shimada SG, Shimada KA, Collins JG (2006) Scratching behavior in mice induced by the proteinase-activated receptor-2 agonist, SLIGRL-NH2. Eur J Pharmacol 530:281–283PubMedCrossRefGoogle Scholar
  14. 14.
    Shinmoto H, Takase M, Naganawa Y, Takano-Ishikawa Y (2009) Production of IgE antibody to Japanese cedar pollen allergen Cry j1 by short term culture of human peripheral blood lymphocytes. Hum Antibodies 18:41–43PubMedGoogle Scholar
  15. 15.
    Sone T, Komiyama N, Shimizu K, Kusakabe T, Morikubo K, Kino K (1994) Cloning and sequencing of cDNA coding for Cry j I, a major allergen of Japanese cedar pollen. Biochem Biophys Res Commun 199:619–625PubMedCrossRefGoogle Scholar
  16. 16.
    Tanaka M, Okada M, Zhen YX, Inamura N, Kitano T, Shirai S, Sakamoto K, Inamura T, Tagami H (1998) Decreased hydration state of the stratum corneum and reduced amino acid content of the skin surface in patients with seasonal allergic rhinitis. Br J Dermatol 139:618–621PubMedCrossRefGoogle Scholar
  17. 17.
    Vinhas R, Cortes L, Cardoso I, Mendes VM, Manadas B, Todo-Bom A, Pires E, Veríssimo P (2011) Pollen proteases compromise the airway epithelial barrier through degradation of transmembrane adhesion proteins and lung bioactive peptides. Allergy 66:1088–1098PubMedCrossRefGoogle Scholar
  18. 18.
    Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, Bautista DM (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci 14:595–602PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Junichi Kumamoto
    • 1
    • 3
  • Moe Tsutsumi
    • 2
  • Makiko Goto
    • 1
    • 2
  • Masaharu Nagayama
    • 1
    • 3
  • Mitsuhiro Denda
    • 1
    • 2
    Email author
  1. 1.Japan Science and Technology Agency, CRESTKawaguchiJapan
  2. 2.Shiseido Research CenterYokohamaJapan
  3. 3.Research Institute for Electronic ScienceHokkaido UniversitySapporoJapan

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