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Synthetic oligonucleotides as modulators of inflammation
Author(s) -
Klinman Dennis,
Shirota Hidekazu,
Tross Debra,
Sato Takashi,
Klaschik Sven
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1107775
Subject(s) - proinflammatory cytokine , biology , cpg oligodeoxynucleotide , immune system , inflammation , oligonucleotide , immunology , autoimmunity , cpg site , cancer research , microbiology and biotechnology , dna , gene expression , gene , biochemistry , dna methylation
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs mimic the immunostimulatory activity of bacterial DNA. CpG ODN directly stimulate human B cells and plasmacytoid dendritic cells, promote the production of Th1 and proinflammatory cytokines, and trigger the maturation/activation of professional APC. CpG ODN are finding use in the treatment of cancer, allergy, and infection. In contrast, ODN containing multiple TTAGGG motifs mimic the immunosuppressive activity of self‐DNA, down‐regulating the production of proinflammatory and Th1 cytokines. Preclinical studies suggest that “suppressive” ODN may slow or prevent diseases characterized by pathologic immune stimulation, including autoimmunity and septic shock. Extensive studies in animal models suggest that the therapeutic value of CpG and TTAGGG ODN may be optimized by early administration.