title: Interleukin-1α is the major alarmin of lung epithelial cells released during photodynamic therapy to induce inflammatory mediators in fibroblasts.
abstract: BACKGROUND
  Photodynamic therapy (PDT) causes tissue damage that initiates a local inflammatory response. Post-PDT reactions are considered to assist in mobilising the immune system thereby affecting tumour recurrence. The initiating process of the PDT-dependent tissue reaction remains to be determined.
  
  
  METHODS
  Primary cultures of human lung cells were established. The photoreaction mediated by pyropheophorbide-a, at specific subcellular sites and levels resulting in the release of alarmins by epithelial cells (Eps), was defined by immunoblot analyses and expression profiling. The activity of Ep-derived factors to stimulate expression of proinflammatory mediators, including IL-6, and to enhance neutrophil binding by fibroblasts (Fbs) was determined by functional bioassays.
  
  
  RESULTS
  Epithelial cells release IL-1β as the primary Fb-stimulatory activity under basal conditions. Intracellular IL-1α, externalised following photoreaction, accounts for most of the PDT-mediated Fb activation. Expression of IL-1 is subject to increase or loss during oncogenic transformation resulting in altered alarmin functions mobilisable by PDT. Photoreaction by a cell surface-bound photosensitiser (PS) is 10-fold more effective than PSs localised to mitochondria or lysosomes. High-dose intracellular, but not cell surface, photoreaction inactivates IL-1 and reduces Fb stimulation.
  
  
  CONCLUSIONS
  These in vitro data suggest that the subcellular site and intensity of photoreaction influence the magnitude of the stromal cell response to the local damage and, in part, support the relationship of PDT dose and level of post-PDT inflammatory response observed in vivo.
authors.affiliation: Departments of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Tracy
authors.forename: M J
authors.initials: MJ
authors.lastname: Bowman
authors.forename: B W
authors.initials: BW
authors.lastname: Henderson
authors.forename: H
authors.initials: H
authors.lastname: Baumann
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010778:Photochemotherapy / Q000379:methods*; D051381:Rats
chemical_list: D018836:Inflammation Mediators; D053582:Interleukin-1alpha