title: 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.
authors.affiliation: Department of Dermatology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: I-Hsin
authors.initials: IH
authors.lastname: Kuo
authors.forename: Amanda
authors.initials: A
authors.lastname: Carpenter-Mendini
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Laura Y
authors.initials: LY
authors.lastname: McGirt
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Ivanov
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Borkowski
authors.forename: Kenshi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Donald Y
authors.initials: DY
authors.lastname: Leung
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
authors.forename: Anna
authors.initials: A
authors.lastname: De Benedetto
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Beck
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D052816:Foreskin / Q000166:cytology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010457:Peptidoglycan / Q000494:pharmacology; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D004561:Transcutaneous Electric Nerve Stimulation; D014945:Wound Healing / Q000502:physiology
chemical_list: D057134:Antibodies, Neutralizing; D001426:Bacterial Proteins; D010457:Peptidoglycan; D012333:RNA, Messenger; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2