CpG oligodeoxynucleotides induce cyclooxygenase-2 in human B lymphocytes: implications for adjuvant activity and antibody production.
Synthetic CpG oligodeoxynucleotides (ODN), similar to DNA sequences found in certain microorganisms, have shown promise as adjuvants for humans by enhancing immune responses. Since antibodies are often indicators of successful vaccination, it is important to understand how CpG ODNs affect human B cells and influence antibody production. Treatment of human B cells with synthetic CpG ODN sequences increased both steady-state Cox-2 mRNA levels and protein expression. B cell receptor stimulation in concert with CpG ODN treatment induced Cox-2 expression and production of prostaglandin E(2), well above that seen with CpG ODN alone. Importantly, CpG-induced human B cell IgM and IgG production was attenuated by dual Cox-1/Cox-2 inhibitors and Cox-2-selective inhibitors. Our findings support a key role for CpG ODN-induced human B cell Cox-2 in the production of IgM and IgG antibodies, revealing that drugs that attenuate Cox-2 activity have the potential to reduce optimal antibody response to adjuvants/vaccination.
Bernard
Matthew P
MP
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Phipps
Richard P
RP
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D015153:Blotting, Western; D002738:Chloroquine / Q000494:pharmacology; D018899:CpG Islands / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000276:immunology; D004790:Enzyme Induction; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D016130:Immunophenotyping; D007213:Indomethacin / Q000494:pharmacology; D008213:Lymphocyte Activation; D009841:Oligonucleotides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000276:Adjuvants, Immunologic; D052246:Cyclooxygenase 2 Inhibitors; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009841:Oligonucleotides; D011720:Pyrazoles; D012333:RNA, Messenger; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; D002738:Chloroquine; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D007213:Indomethacin