Tumor necrosis factor-alpha (TNF) regulates the expression of ICAM-1 predominantly through TNF receptor 1 after chronic constriction injury of mouse sciatic nerve.
Proinflammatory cytokines like tumor necrosis factor-alpha (TNF) contribute to Wallerian degeneration by enhancing the adhesion of leukocytes to the endothelium through increased expression of adhesion molecules. Here we studied the influence of TNF and TNF receptors (TNFR) on intercellular adhesion molecule-1 (ICAM-1) and macrophage influx following chronic constrictive injury (CCI) in mice by three different paradigms: (1) C57BL/Wld mice with delayed TNF up-regulation, (2) in vivo inhibition of TNFR1 and TNFR2 by neutralizing antibodies, and (3) three different types of mice with a genetic deficiency for TNFR. C57BL/Wld mice with a delayed macrophage influx had a delayed increase of ICAM-1 compared to control mice. In vivo inhibition of both TNFR significantly impaired macrophage recruitment; however, treatment with anti-TNFR1 antibodies increased endoneurial ICAM-1 expression. In TNFR1 and TNFR1+2, but not TNFR2-deficient mice, endoneurial ICAM-1 expression was significantly reduced, which correlated with prolonged Wallerian degeneration in TNFR1-deficient mice 2 weeks after CCI. Our data support the hypothesis that TNF regulates the expression of ICAM-1 predominantly through TNFR1.
Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. mschaefers@ucsd.edu
Maria
M
Schäfers
Christine
C
Schmidt
Carola
C
Vogel
Klaus V
KV
Toyka
Claudia
C
Sommer
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009408:Nerve Compression Syndromes / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D014855:Wallerian Degeneration / Q000378:metabolism
D000906:Antibodies; D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1