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CpG Oligodeoxynucleotides Induce Cyclooxygenase-2 in Human B Lymphocytes: Implications for Adjuvant Activity and Antibody Production

机译:CpG寡脱氧核苷酸在人B淋巴细胞中诱导环氧合酶-2:对佐剂活性和抗体产生的影响。

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摘要

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 ODN affects human B cells and influences 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 E2, 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.
机译:类似于某些微生物中发现的DNA序列的合成CpG寡脱氧核苷酸(ODN)已显示出有望通过增强免疫反应作为人类的佐剂。由于抗体通常是成功接种疫苗的指标,因此了解CpG ODN如何影响人B细胞并影响抗体产生非常重要。用合成的CpG ODN序列处理人B细胞可增加稳态Cox-2 mRNA水平和蛋白质表达。 B细胞受体刺激与CpG ODN协同治疗可诱导Cox-2表达和前列腺素E2产生,远高于单独使用CpG ODN所见。重要的是,双重Cox-1 / Cox-2抑制剂和Cox-2选择性抑制剂减弱了CpG诱导的人B细胞IgM和IgG的产生。我们的发现支持CpG ODN诱导的人B细胞Cox-2在IgM和IgG抗体产生中的关键作用,揭示了减弱Cox-2活性的药物有可能降低对佐剂/疫苗的最佳抗体反应。

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