Intercellular adhesion molecule-1: a consistent inflammatory marker of the cutaneous radiation reaction both in vitro and in vivo.
BACKGROUND
Radiation damage to skin is a key diagnostic and prognostic parameter for patients accidentally exposed to radiation. Moreover, skin is a target organ for crucial side-effects of routine radiotherapy. The pathophysiology of the cutaneous radiation reaction is in many respects still unknown. The acute inflammatory radiation reaction of skin has been shown to involve alterations in cell-cell and cell-matrix interactions, which are mediated by cellular adhesion molecules.


OBJECTIVE
To evaluate the effect of ionizing radiation on intercellular adhesion molecule-1 (ICAM-1) expression in human skin cells.


METHODS
Dermal monolayer cells, a three-dimensional skin model and skin biopsies were investigated for ICAM-1 expression after ionizing radiation using flow cytometry, quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. ICAM-1 expression in monolayer cells pretreated with protein kinase inhibitors and dexamethasone prior to irradiation was analysed by flow cytometry.


RESULTS
Using different sources of skin cells, we demonstrated a consistent upregulation of both ICAM-1 mRNA and protein expression by ionizing radiation. Blocking experiments revealed that tumour necrosis factor-alpha, another ICAM-1 inducer, does not account for the effect of radiation. Radiation-induced upregulation of ICAM-1 expression was significantly attenuated by inhibitors to protein kinase C, mitogen-activated protein (MAP) ERK kinase, p38 MAP kinase and phosphatidylinositol 3-kinase. The anti-inflammatory agent dexamethasone suppressed the effect of radiation on ICAM-1 expression, suggesting its usefulness to treat the cutaneous radiation reaction.


CONCLUSIONS
Our data suggest that ICAM-1 is a consistent inflammatory parameter of the cutaneous radiation reaction both in vitro and in vivo that might provide new therapeutic options for diagnosis and treatment of effects of radiation.
Müller
K
K
Bundeswehr Institute of Radiobiology, Neuherbergstr. 11, D-80937 Munich, Germany.
Köhn
F-M
FM
Port
M
M
Abend
M
M
Molls
M
M
Ring
J
J
Meineke
V
V
D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics; D011832:Radiation Injuries / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology / Q000528:radiation effects; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone