PMID- 10051633
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 5
DP  - 1999 Mar 2
TI  - Activation of target-tissue immune-recognition molecules by double-stranded
      polynucleotides.
PG  - 2285-90
AB  - Abnormal expression of major histocompatibility complex (MHC) class I and class
      II in various tissues is associated with autoimmune disease. Autoimmune responses
      can be triggered by viral infections or tissue injuries. We show that the ability
      of a virus or a tissue injury to increase MHC gene expression is duplicated by
      any fragment of double-stranded (ds) DNA or dsRNA introduced into the cytoplasm
      of nonimmune cells. Activation is sequence-independent, is induced by ds
      polynucleotides as small as 25 bp in length, and is not duplicated by
      single-stranded polynucleotides. In addition to causing abnormal MHC expression, 
      the ds nucleic acids increase the expression of genes necessary for antigen
      processing and presentation: proteasome proteins (e.g., LMP2), transporters of
      antigen peptides; invariant chain, HLA-DM, and the costimulatory molecule B7.1.
      The mechanism is different from and additive to that of gamma-interferon
      (gammaIFN), i.e., ds polynucleotides increase class I much more than class II,
      whereas gammaIFN increases class II more than class I. The ds nucleic acids also 
      induce or activate Stat1, Stat3, mitogen-activated protein kinase, NF-kappaB, the
      class II transactivator, RFX5, and the IFN regulatory factor 1 differently from
      gammaIFN. CpG residues are not responsible for this effect, and the action of the
      ds polynucleotides could be shown in a variety of cell types in addition to
      thyrocytes. We suggest that this phenomenon is a plausible mechanism that might
      explain how viral infection of tissues or tissue injury triggers autoimmune
      disease; it is potentially relevant to host immune responses induced during gene 
      therapy.
FAU - Suzuki, K
AU  - Suzuki K
AD  - Cell Regulation Section, Metabolic Diseases Branch, National Institute of
      Diabetes and Digestive and Kidney Diseases, National Institutes of Health,
      Bethesda, MD 20892, USA.
FAU - Mori, A
AU  - Mori A
FAU - Ishii, K J
AU  - Ishii KJ
FAU - Saito, J
AU  - Saito J
FAU - Singer, D S
AU  - Singer DS
FAU - Klinman, D M
AU  - Klinman DM
FAU - Krause, P R
AU  - Krause PR
FAU - Kohn, L D
AU  - Kohn LD
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA, Viral)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EBV-associated membrane antigen, Epstein-Barr virus)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Double-Stranded)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Stat1 protein, rat)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Stat3 protein, rat)
RN  - 0 (Trans-Activators)
RN  - 0 (Viral Matrix Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Line
MH  - DNA, Viral/*immunology
MH  - DNA-Binding Proteins/metabolism
MH  - Gene Expression Regulation/*immunology
MH  - Genes, MHC Class I
MH  - Genes, MHC Class II
MH  - Interferon-gamma/immunology
MH  - *Major Histocompatibility Complex
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - RNA, Double-Stranded/immunology
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT1 Transcription Factor
MH  - STAT3 Transcription Factor
MH  - Simplexvirus/*immunology
MH  - Thyroid Gland
MH  - Trans-Activators/metabolism
MH  - Transfection
MH  - Viral Matrix Proteins/immunology
PMC - PMC26775
EDAT- 1999/03/03 00:00
MHDA- 1999/03/03 00:01
CRDT- 1999/03/03 00:00
PHST- 1999/03/03 00:00 [pubmed]
PHST- 1999/03/03 00:01 [medline]
PHST- 1999/03/03 00:00 [entrez]
AID - 10.1073/pnas.96.5.2285 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2285-90. doi: 10.1073/pnas.96.5.2285.