title: Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) plays a key role in allergic diseases, such as atopic dermatitis (AD) and asthma. TSLP is highly expressed by keratinocytes in skin lesions of patients with AD, but environmental triggers for its release from keratinocytes with endogenous factors are not well understood. Patients with AD, in whom allergic sensitization is already established, are susceptible to viral dissemination.
  
  
  OBJECTIVE
  We investigated TSLP's release from primary human keratinocytes stimulated with a Toll-like receptor (TLR) 3 ligand, polyinosinic-polycytidylic acid, which mimics viral double-stranded RNA (dsRNA), and its modulation by cytokines.
  
  
  METHODS
  Primary human keratinocytes were stimulated with TLR ligands, cytokines, or both. TSLP released into culture supernatants was measured by means of ELISA.
  
  
  RESULTS
  Stimulation of keratinocytes with dsRNA induced release of TSLP and upregulated gene expression of TSLP and other cytokines and chemokines. The release of TSLP was enhanced by the addition of IL-4, IL-13, and/or TNF-alpha. With or without the T(H)2/TNF cytokines, the dsRNA-induced release of TSLP was upregulated by IFN-alpha and IFN-beta and suppressed by IFN-gamma, TGF-beta, or IL-17.
  
  
  CONCLUSIONS
  The effect of the TLR3 ligand on keratinocytes suggests contribution of viral dsRNA to skin inflammations under the influence of a cytokine milieu. The results imply that viral dsRNA and a T(H)2 cytokine milieu might promote T(H)2-type inflammation through an induction of TSLP expression, suggesting that a vicious cycle exists between AD with T(H)2-type inflammation and viral infections and a possible blockade of this cycle by other cytokine milieus provided by cells, such as T(H)1, regulatory T, and T(H)17 cells.
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takai
authors.forename: Tuan Anh
authors.initials: TA
authors.lastname: Le
authors.forename: Seiji
authors.initials: S
authors.lastname: Kamijo
authors.forename: Xiao Ling
authors.initials: XL
authors.lastname: Wang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ushio
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Hara
authors.forename: Junko
authors.initials: J
authors.lastname: Kawasaki
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Vu
authors.forename: Takasuke
authors.initials: T
authors.lastname: Ogawa
authors.forename: Hendra
authors.initials: H
authors.lastname: Gunawan
authors.forename: Shigaku
authors.initials: S
authors.lastname: Ikeda
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D001249:Asthma / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007369:Interferon Inducers / Q000276:immunology / Q000494:pharmacology*; D008024:Ligands; D011070:Poly I-C / Q000276:immunology* / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000276:immunology / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007369:Interferon Inducers; D008024:Ligands; D012330:RNA, Double-Stranded; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C; D000094632:Thymic Stromal Lymphopoietin