CpG-DNA upregulates the major acute-phase proteins SAA and SAP.
The acute-phase response is an immediate reaction of the host against invading microorganisms. We show here that oligodeoxynucleotides (ODNs) containing a CpG motif rapidly induce the major murine acute-phase proteins in vivo, i.e. serum amyloid A (SAA) and serum amyloid P (SAP). Serum levels of these proteins are elevated within 12 h and peak at 24 h after the injection of CpG-ODN or endotoxin. Liver cells produce the proteins with the same kinetics. Injection of interleukin 6 (IL-6), IL-1beta and tumour necrosis factor alpha (TNF-alpha) induces SAA and SAP in vivo, but the CpG-ODN-mediated induction does not depend on the presence of the TNF receptor p55, as the acute-phase response in TNF receptor p55-deficient mice does not differ from that of wild-type mice. Aside from CpG-ODN, bacterial genomic DNA also induces the acute-phase response in LPS-resistant C3H/Hej mice. The induction of the major acute-phase proteins SAA and SAP is blocked by the simultaneous injection of CpG-ODN together with D-galactosamine (D-GalN). As D-GalN sensitizes the host for the toxic effects of TNF-alpha, a possible mechanism could be the prevention of synthesis of the major acute-phase proteins SAA and SAP.
Schmidt
U
U
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Germany.
Wagner
H
H
Miethke
T
T
D000210:Acute-Phase Reaction / Q000097:blood / Q000139:chemically induced*; D000818:Animals; D001053:Apolipoproteins / Q000032:analysis / Q000378:metabolism*; D004269:DNA, Bacterial / Q000633:toxicity*; D004731:Endotoxins / Q000633:toxicity; D007375:Interleukin-1 / Q000633:toxicity; D015850:Interleukin-6 / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000633:toxicity*; D010446:Peptide Fragments / Q000633:toxicity; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity; D015854:Up-Regulation
D001053:Apolipoproteins; C408982:CPG-oligonucleotide; D004269:DNA, Bacterial; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D018124:Receptors, Tumor Necrosis Factor; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; C066650:tumor necrosis factor alpha (36-68)