title: Radiation-induced mast cell mediators differentially modulate chemokine release from dermal fibroblasts.
abstract: BACKGROUND
  Ionizing radiation has been demonstrated to result in degranulation of dermal mast cells. Chemokines are thought to play a crucial role in the early phase of the cutaneous radiation reaction. In human skin, mast cells are located in close proximity to dermal fibroblasts, which thus are a potential target for the action of mast cell mediators.
  
  
  OBJECTIVE
  In this study, we evaluated the effects of mast cell-derived histamine, serotonin, tumour necrosis factor (TNF)-α and tryptase on chemokine release from dermal fibroblasts.
  
  
  METHODS
  Human mast cells (HMC-1) were investigated for histamine release and cytokine production after ionizing radiation using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Receptor expression on human fetal foreskin fibroblasts (HFFF2) and human adult skin fibroblasts (HDFa) was examined by flow cytometry. Chemokine mRNA and protein expression were analyzed by gene array and ELISA, respectively.
  
  
  RESULTS
  Ionizing radiation significantly increased histamine release and cytokine expression by HMC-1 cells. Receptors for histamine, serotonin, TNF-α and tryptase were detected both in HFFF2 and in HDFa cells. Dermal fibroblasts constitutively expressed distinct sets of chemokine mRNA. Mast cell mediators differentially affected the release of chemokines CCL8, CCL13, CXCL4 and CXCL6 by fibroblasts.
  
  
  CONCLUSIONS
  Our data suggest that radiation-induced mast cell mediators have a tremendous impact on inflammatory cell recruitment into irradiated skin. We postulate the activation of mast cells to be an initial key event in the cutaneous radiation reaction, which might offer promising targets for treatment of both normal tissue side effects in radiation therapy and radiation injuries.
authors.affiliation: Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany. kerstin2mueller@bundeswehr.org
authors.forename: Kerstin
authors.initials: K
authors.lastname: Müller
authors.forename: Viktor
authors.initials: V
authors.lastname: Meineke
mesh_terms: D000375:Aging / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D020405:Dermis / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D012701:Serotonin / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D006632:Histamine; D053802:Tryptases