Archives of Dermatological Research

, Volume 304, Issue 1, pp 65–71 | Cite as

Increased skin barrier disruption by sodium lauryl sulfate in mice expressing a constitutively active STAT6 in T cells

  • Sonia C. DaSilva
  • Ravi P. Sahu
  • Raymond L. Konger
  • Susan M. Perkins
  • Mark H. Kaplan
  • Jeffrey B. Travers
Short Communication

Abstract

Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease that affects 10–20% of children and 1–3% of adults worldwide. Recent studies have indicated that the ability of Th2 cytokines, such as interleukin-4 (IL-4) to regulate skin barrier function may be a predisposing factor for AD development. The present studies examined the ability of increased Th2 activity to affect cutaneous barrier function in vivo and epidermal thickening. Mice that express a constitutively active Signal Transducer and Activator of Transcription 6 (STAT6VT) have increased Th2 cells and a predisposition to allergic inflammation were used in these studies, they demonstrate that topical treatment with the irritant sodium lauryl sulfate (SLS) caused increased transepidermal water loss and epidermal thickening in STAT6VT mice over similarly treated wild-type mice. The proliferation marker Ki-67 was increased in the epidermis of STAT6VT compared to the wild-type mice. However, these differences do not appear to be linked to the addition of an irritant as control-treated STAT6VT skin also exhibited elevated Ki-67 levels, suggesting that the increased epidermal thickness in SLS-treated STAT6VT mice is primarily driven by epidermal cell hypertrophy rather than an increase in cellular proliferation. Our results suggest that an environment with increased Th2 cytokines results in abnormal responses to topical irritants.

Keywords

Atopic dermatitis Interleukin-4 STAT6 V547A/T548A mutation Transepidermal water loss T-helper type 2 cells 

References

  1. 1.
    Anderson C, Sundberg K, Groth O (1986) Animal model for assessment of skin irritancy. Contact Dermatitis 15:143–151. doi:10.1111/j.1600-0536.1986.tb01315.x PubMedCrossRefGoogle Scholar
  2. 2.
    Bruns HA, Schindler U, Kaplan MH (2003) Expression of a constitutively active Stat6 in vivo alters lymphocyte homeostasis with distinct effects in T and B cells. J Immunol 170:3478–3487PubMedGoogle Scholar
  3. 3.
    Daniel C, Salvekar A, Schindler U (2000) A gain-of-function mutation in STAT6. J Biol Chem 275:14255–14259. doi:C000129200 PubMedCrossRefGoogle Scholar
  4. 4.
    De Jongh CM, Verberk MM, Withagen CE, Jacobs JJ, Rustemeyer T, Kezic S (2006) Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate. Contact Dermatitis 54:325–333. doi:10.1111/j.0105-1873.2006.00848.x PubMedCrossRefGoogle Scholar
  5. 5.
    Denda M, Wood LC, Emami S, Calhoun C, Brown BE, Elias PM, Feingold KR (1996) The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss. Arch Dermatol Res 288:230–238. doi:10.1007/BF02530090 PubMedCrossRefGoogle Scholar
  6. 6.
    Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715PubMedGoogle Scholar
  7. 7.
    Leung DY, Bieber T (2003) Atopic dermatitis. Lancet 361:151–160. doi:S0140-6736(03)12193-9 PubMedCrossRefGoogle Scholar
  8. 8.
    Li LF, Fiedler VC, Kumar R (1999) Induction of hair growth by skin irritants and its relation to skin protein kinase C isoforms. Br J Dermatol 140:616–623. doi:10.1046/j.1365-2133.1999.02759.x PubMedCrossRefGoogle Scholar
  9. 9.
    Loden M (1995) Biophysical properties of dry atopic and normal skin with special reference to effects of skin care products. Acta Derm Venereol Suppl (Stockh) 192:1–48Google Scholar
  10. 10.
    Nielsen JB (2000) Effects of four detergents on the in vitro barrier function of human skin. Int J Occup Environ Health 6:143–147PubMedGoogle Scholar
  11. 11.
    Patil S, Singh P, Sarasour K, Maibach H (1995) Quantification of sodium lauryl sulfate penetration into the skin and underlying tissue after topical application—pharmacological and toxicological implications. J Pharm Sci 84:1240–1244PubMedCrossRefGoogle Scholar
  12. 12.
    Sehra S, Tuana FMB, Holbreich M, Mousdicas N, Tepper RS, Chang CH, Travers JB, Kaplan MH (2008) Scratching the surface: towards understanding the pathogenesis of atopic dermatitis. Crit Rev Immunol 28:15–43PubMedGoogle Scholar
  13. 13.
    Sehra S, Yao Y, Howell MD, Nguyen ET, Kansas GS, Leung DY, Travers JB, Kaplan MH (2010) IL-4 regulates skin homeostasis and the predisposition toward allergic skin inflammation. J Immunol 184:3186–3190. doi:10.4049/jimmunol.0901860 PubMedCrossRefGoogle Scholar
  14. 14.
    Werner Y, Lindberg M (1985) Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis. Acta Derm Venereol 65:102–105PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sonia C. DaSilva
    • 2
  • Ravi P. Sahu
    • 2
  • Raymond L. Konger
    • 2
    • 3
  • Susan M. Perkins
    • 1
  • Mark H. Kaplan
    • 4
  • Jeffrey B. Travers
    • 2
    • 4
    • 5
    • 6
    • 7
  1. 1.Department of BiostaticsIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of DermatologyIndiana University School of MedicineIndianapolisUSA
  3. 3.Department of Pathology and Laboratory MedicineIndiana University School of MedicineIndianapolisUSA
  4. 4.Department of Pediatrics and the H.B Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisUSA
  5. 5.Department of Pharmacology and ToxicologyIndiana University School of MedicineIndianapolisUSA
  6. 6.Indiana University School of MedicineIndianapolisUSA
  7. 7.The Richard L. Roudebush V.A. Medical CenterIndiana University School of MedicineIndianapolisUSA

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