TNF alpha and IL-1beta mediate intercellular adhesion molecule-1 induction via microglia-astrocyte interaction in CNS radiation injury.
Radiation injury to the central nervous system (CNS) results in glial activation accompanied by expression of pro-inflammatory cytokines and adhesion molecules. In this study we demonstrate intercellular adhesion molecule-1 (ICAM-1) induction in the irradiated mouse brain at the mRNA and protein levels. Immunocytochemical analysis revealed that ICAM-1 protein was primarily expressed in endothelial cells and microglia. In vitro, ionizing radiation significantly induces TNF alpha, IL-1beta and ICAM-1 mRNA in primary microglia cultures. Interestingly, although ionizing radiation activated primary astrocyte cultures, it did not induce ICAM-1 expression. However, exposure of astrocytes to conditioned medium collected from irradiated microglia resulted in ICAM-1 induction, which was abrogated when the conditioned medium was pre-incubated with neutralizing antibodies raised against murine TNF alpha and IL-1beta. These results indicate that pro-inflammatory cytokines may be necessary for ICAM-1 expression in astrocytes in CNS radiation injury.
Kyrkanides
S
S
Department of Neurobiology and Anatomy, School of Medicine and Dentistry, University of Rochester, NY 14642, USA.
Olschowka
J A
JA
Williams
J P
JP
Hansen
J T
JT
O'Banion
M K
MK
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2; D017931:DNA Primers; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D017628:Microglia / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects; D010544:Peroxidases / Q000235:genetics / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000276:immunology; D011833:Radiation Injuries, Experimental / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D017077:Culture Media, Conditioned; D017931:DNA Primers; D007375:Interleukin-1; D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases