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Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair.

Abstract

Atopic dermatitis (AD) is characterized by epidermal tight junction (TJ) defects and a propensity for Staphylococcus aureus skin infections. S. aureus is sensed by many pattern recognition receptors, including Toll-like receptor 2 (TLR2). We hypothesized that an effective innate immune response will include skin barrier repair, and that this response is impaired in AD subjects. S. aureus-derived peptidoglycan (PGN) and synthetic TLR2 agonists enhanced TJ barrier and increased expression of TJ proteins, claudin-1 (CLDN1), claudin-23 (CLDN23), occludin, and Zonulae occludens 1 (ZO-1) in primary human keratinocytes. A TLR2 agonist enhanced skin barrier recovery in human epidermis wounded by tape stripping. Tlr2(-/-) mice had a delayed and incomplete barrier recovery following tape stripping. AD subjects had reduced epidermal TLR2 expression as compared with nonatopic subjects, which inversely correlated (r=-0.654, P=0.0004) with transepidermal water loss (TEWL). These observations indicate that TLR2 activation enhances skin barrier in murine and human skin and is an important part of a wound repair response. Reduced epidermal TLR2 expression observed in AD patients may have a role in their incompetent skin barrier.

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  • Authors+Show Affiliations

    ,

    Department of Dermatology, University of Rochester Medical Center, Rochester, NY, USA.

    , , , , , , , , , , ,

    Source

    MeSH

    Animals
    Antibodies, Neutralizing
    Bacterial Proteins
    Dermatitis, Atopic
    Epidermis
    Female
    Foreskin
    Humans
    Keratinocytes
    Male
    Mice
    Mice, Inbred C57BL
    Mice, Knockout
    Peptidoglycan
    Permeability
    RNA, Messenger
    Tight Junctions
    Toll-Like Receptor 1
    Toll-Like Receptor 2
    Transcutaneous Electric Nerve Stimulation
    Wound Healing

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    23223142

    Citation

    Kuo, I-Hsin, et al. "Activation of Epidermal Toll-like Receptor 2 Enhances Tight Junction Function: Implications for Atopic Dermatitis and Skin Barrier Repair." The Journal of Investigative Dermatology, vol. 133, no. 4, 2013, pp. 988-98.
    Kuo IH, Carpenter-Mendini A, Yoshida T, et al. Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair. J Invest Dermatol. 2013;133(4):988-98.
    Kuo, I. H., Carpenter-Mendini, A., Yoshida, T., McGirt, L. Y., Ivanov, A. I., Barnes, K. C., ... Beck, L. A. (2013). Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair. The Journal of Investigative Dermatology, 133(4), pp. 988-98. doi:10.1038/jid.2012.437.
    Kuo IH, et al. Activation of Epidermal Toll-like Receptor 2 Enhances Tight Junction Function: Implications for Atopic Dermatitis and Skin Barrier Repair. J Invest Dermatol. 2013;133(4):988-98. PubMed PMID: 23223142.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair. AU - Kuo,I-Hsin, AU - Carpenter-Mendini,Amanda, AU - Yoshida,Takeshi, AU - McGirt,Laura Y, AU - Ivanov,Andrei I, AU - Barnes,Kathleen C, AU - Gallo,Richard L, AU - Borkowski,Andrew W, AU - Yamasaki,Kenshi, AU - Leung,Donald Y, AU - Georas,Steve N, AU - De Benedetto,Anna, AU - Beck,Lisa A, Y1 - 2012/12/06/ PY - 2012/12/11/entrez PY - 2012/12/12/pubmed PY - 2013/5/8/medline SP - 988 EP - 98 JF - The Journal of investigative dermatology JO - J. Invest. Dermatol. VL - 133 IS - 4 N2 - Atopic dermatitis (AD) is characterized by epidermal tight junction (TJ) defects and a propensity for Staphylococcus aureus skin infections. S. aureus is sensed by many pattern recognition receptors, including Toll-like receptor 2 (TLR2). We hypothesized that an effective innate immune response will include skin barrier repair, and that this response is impaired in AD subjects. S. aureus-derived peptidoglycan (PGN) and synthetic TLR2 agonists enhanced TJ barrier and increased expression of TJ proteins, claudin-1 (CLDN1), claudin-23 (CLDN23), occludin, and Zonulae occludens 1 (ZO-1) in primary human keratinocytes. A TLR2 agonist enhanced skin barrier recovery in human epidermis wounded by tape stripping. Tlr2(-/-) mice had a delayed and incomplete barrier recovery following tape stripping. AD subjects had reduced epidermal TLR2 expression as compared with nonatopic subjects, which inversely correlated (r=-0.654, P=0.0004) with transepidermal water loss (TEWL). These observations indicate that TLR2 activation enhances skin barrier in murine and human skin and is an important part of a wound repair response. Reduced epidermal TLR2 expression observed in AD patients may have a role in their incompetent skin barrier. SN - 1523-1747 UR - https://www.unboundmedicine.com/medline/citation/23223142/Activation_of_epidermal_toll_like_receptor_2_enhances_tight_junction_function:_implications_for_atopic_dermatitis_and_skin_barrier_repair_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-202X(15)36206-0 DB - PRIME DP - Unbound Medicine ER -