Involvement of nuclear factor-kappaB in a murine model for the acute form of autoimmune-like toxic oil syndrome.
The toxic oil syndrome (TOS) represents an exogenously induced autoimmune disease with acute or chronic symptoms similar to systemic lupus erythematosus or scleroderma. When genetically different mouse strains were exposed to oleic acid anilide (OAA), it was possible to mimic the different syndrome manifestations. The aim of the present study was to examine the role of NF-kappaB/Rel transcription factors in the development of the severe acute wasting disease observed in A/J mice. Within a week of OAA exposure, the A/J, but not B10.S strain, displayed weight loss, cachexia, apathy, reduced activity, and breathing difficulties. In affected A/J mice we observed a marked increase in NF-kappaB activation (p50/p65 dimers) both in splenic T cells and peritoneal macrophages as well as in tissue from aorta and gut. Incubation of splenocytes with OAA in vitro induced a dose-dependent removal of IkappaB-alpha, accompanied by NF-kappaB activation, whereas Sp-1 binding was not affected. Furthermore, we demonstrated the increased expression of the two NF-kappaB target genes IL-6 and IL-1beta in OAA-exposed mice and a transient OAA-induced accumulation of TNFalpha in vitro. This is the first report which implicates NF-kappaB/Rel in acute forms of chemically induced autoimmune-like disease and may serve as a paradigm for the involvement of this transcriptional system in acute processes associated with autoimmunity, suggesting possible avenues of therapeutic intervention.
Bell
S A
SA
Department of Dermatology, Ludwig-Maximilians-University, Munich, 80337, Germany.
Page
S
S
Baumgartner
B
B
Berking
C
C
Haas
M
M
Eisele
T
T
Neumeier
D
D
Brand
K
K
D000208:Acute Disease; D000813:Anilides / Q000633:toxicity*; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced*; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D020672:I-kappa B Proteins; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008805:Mice, Inbred A; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis*; D052002:NF-kappa B p50 Subunit; D009829:Oleic Acids / Q000633:toxicity*; D009928:Organ Specificity; D010938:Plant Oils / Q000633:toxicity*; D012260:Ribonucleases / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013577:Syndrome; D013601:T-Lymphocytes / Q000187:drug effects; D051996:Transcription Factor RelA
D000813:Anilides; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606205:Nfkbia protein, mouse; D009829:Oleic Acids; D010938:Plant Oils; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C038731:oleoylanilide; D012260:Ribonucleases