title: Thymic stromal lymphopoietin induction by skin irritation is independent of tumour necrosis factor-α, but supported by interleukin-1.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) is an extensively studied cytokine linked to the pathogenesis of allergic diseases, but the inherent activities behind TSLP expression are not well defined.
  
  
  OBJECTIVE
  To explore the conditions favourable to TSLP induction outside of a typically allergic set-up and determine the associated mechanisms, and to assess whether TSLP is similarly controlled in murine and human skin.
  
  
  METHODS
  A combination of primary keratinocytes, skin explants/epidermal sheets and in vivo strategies was employed. The skin of wild-type and tumour necrosis factor knockout (TNF-/-) mice was subjected to acute irritation. Cells and specimens were stimulated with a range of TSLP inducers in the presence or absence of neutralizing antibodies. TSLP was quantitated by quantitative reverse-transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry.
  
  
  RESULTS
  In addition to cytokines, skin irritation brought about by various causes (e.g. shaving, scratching and chemical perturbation) elicited uniformly high-level production of TSLP, which entered the circulatory system. Despite the potency of TNF-α as an in vitro TSLP inducer, the use of TNF-/- mice revealed that this mechanism was completely independent of endogenous TNF-α. Conversely, irritation-elicited TSLP depended on interleukin (IL)-1, which had a more pronounced influence in human skin than in murine skin. Murine and human skin differed considerably regarding TSLP regulation.
  
  
  CONCLUSIONS
  Thymic stromal lymphopoietin is a general responder to disrupted skin homeostasis and may have a role in triggering the alarm system of the skin. TSLP induction is rapid, transient and driven by a mechanism that does not involve TNF-α, but partially relies on the evolutionarily ancient IL-1 system. The irritated skin secretes TSLP into the circulatory system. TSLP regulation varies between species.
authors.affiliation: Klinik für Dermatologie und Allergologie, Allergie-Centrum-Charité, CCM, Charité - Universitätsmedizin, 10117, Berlin, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Kumari
authors.forename: M
authors.initials: M
authors.lastname: Babina
authors.forename: T
authors.initials: T
authors.lastname: Hazzan
authors.forename: M
authors.initials: M
authors.lastname: Worm
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000494:pharmacology; D017453:Dermatitis, Irritant / Q000503:physiopathology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D013501:Surface-Active Agents; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D012967:Sodium Dodecyl Sulfate; D000094632:Thymic Stromal Lymphopoietin