Zhou A, Chen Z, Rummage J A, Jiang H, Kolosov M, Kolosova I, Stewart C A, Leu R W
Oklahoma Medical Research Foundation, Noble Center for Biomedical Research, Oklahoma City 73104-5046, USA.
J Interferon Cytokine Res. 1995 Oct;15(10):897-904. doi: 10.1089/jir.1995.15.897.
Murine macrophages (M phi) are activated either by interferon-gamma (IFN-gamma) or interferon-alpha/beta (IFN-alpha/beta) in combination with bacterial lipopolysaccharide (LPS) to induce synthesis of tumor necrosis factor alpha (TNF-alpha) and nitric oxide synthase (iNOS) mRNA synthesis for generation of tumor cytotoxic nitric oxide (NO). In the present study, the effect of exogenous IFN-gamma on the induction of endogenous mRNA synthesis and secretion of IFN-alpha/beta by murine M phi was investigated. Neutralizing antibodies to IFN-alpha/beta reversed TNF-alpha and NOS mRNA synthesis, as well as nitric oxide (NO)-mediated tumor cytotoxicity. Quantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that treatment of M phi with IFN-gamma induced increases in both IFN-alpha and IFN-beta mRNA synthesis by approximately 2-fold and 10-fold, respectively, which corresponded to a 2-fold increase in secretion of IFN-alpha/beta by ELISA. These data indicate that exogenous IFN-gamma induces endogenous synthesis and secretion of IFN-alpha/beta by M phi, which appears to act in concert with endogenously synthesized TNF-alpha for the autocrine induction of NOS mRNA synthesis.
小鼠巨噬细胞（M phi）可被γ干扰素（IFN-γ）或α/β干扰素（IFN-α/β）与细菌脂多糖（LPS）联合激活，以诱导肿瘤坏死因子α（TNF-α）的合成以及一氧化氮合酶（iNOS）mRNA的合成，从而产生具有肿瘤细胞毒性的一氧化氮（NO）。在本研究中，研究了外源性IFN-γ对小鼠M phi诱导内源性mRNA合成以及分泌IFN-α/β的影响。针对IFN-α/β的中和抗体可逆转TNF-α和NOS mRNA的合成，以及一氧化氮（NO）介导的肿瘤细胞毒性。定量逆转录聚合酶链反应（RT-PCR）显示，用IFN-γ处理M phi可使IFN-α和IFN-β mRNA的合成分别增加约2倍和10倍，这与ELISA检测到的IFN-α/β分泌增加2倍相对应。这些数据表明，外源性IFN-γ可诱导M phi内源性合成并分泌IFN-α/β，其似乎与内源性合成的TNF-α协同作用，以自分泌方式诱导NOS mRNA的合成。
