Saccani S, Polentarutti N, Penton-Rol G, Sims J E, Mantovani A
Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche "Mario Negri", Centro Daniela e Catullo Borgomainerio, 20157 Milano, Italy.
Cytokine. 1998 Oct;10(10):773-80. doi: 10.1006/cyto.1998.0359.
Three molecules, interleukin 1 (IL-1) receptor I (IL-1RI), IL-1 receptor II (IL-1RII or decoy) and IL-1 receptor accessory protein (IL-1R AcP or IL-1RIII), are involved in IL-1 binding and signal transduction. In addition, three homologous genes (T1/ST2, MyD88 and rsc786) have been identified. Expression of the signal transducing type I R and of the decoy type II R in human monocytes is regulated by pro- and anti-inflammatory signals. The present study was designed to evaluate comprehensively how a prototypic pro-inflammatory signal, bacterial lipopolysaccharide (LPS), affects expression of IL-1R family members in mononuclear phagocytes in vitro and in vivo. Resting human monocytes expressed high levels of IL-1RII, IL-1R AcP, MyD88 and rsc786, whereas low levels of IL-1RI and T1/ST2 were present. In vitro exposure to LPS augmented expression of IL-1RI, T1/ST2 and MyD88, whereas it inhibited that of IL-1RII and rsc786. Expression of IL-1R AcP in monocytes was less substantially affected by LPS. The expression of IL-1R family members was also studied in organs of mice given LPS. As expected on the basis of in vitro results, organs (e.g. spleen, lungs and peritoneal exudate cells) from LPS-treated mice showed increased levels of IL-1RI, T1/ST2 and MyD88. Intriguingly, while expression of IL-1RII was inhibited in peritoneal macrophages after LPS, in accordance with in vitro results, increased IL-1RII mRNA was observed in organs such as liver, lungs and spleen. This unexpected effect of LPS was drastically reduced in mice rendered neutropenic by 5-fluorouracil. Therefore, we conclude that the apparent induction of IL-1RII in certain organs of LPS-treated mice is due to recruitment of myeloid cells which express high levels of decoy RII. Therefore, members of IL-1R family are independently and divergently regulated in mononuclear phagocytes exposed to the prototypic pro-inflammatory signal LPS in vitro and in vivo.
白细胞介素1（IL-1）受体I（IL-1RI）、IL-1受体II（IL-1RII或诱饵受体）和IL-1受体辅助蛋白（IL-1R AcP或IL-1RIII）这三种分子参与IL-1的结合和信号转导。此外，还鉴定出了三个同源基因（T1/ST2、MyD88和rsc786）。人单核细胞中信号转导I型受体和诱饵II型受体的表达受促炎和抗炎信号调节。本研究旨在全面评估典型促炎信号细菌脂多糖（LPS）如何在体外和体内影响单核吞噬细胞中IL-1受体家族成员的表达。静息的人单核细胞表达高水平的IL-1RII、IL-1R AcP、MyD88和rsc786，而IL-1RI和T1/ST2的水平较低。体外暴露于LPS可增加IL-1RI、T1/ST2和MyD88的表达，而抑制IL-1RII和rsc786的表达。LPS对单核细胞中IL- AcP表达的影响较小。还研究了给予LPS的小鼠器官中IL-1受体家族成员的表达。根据体外实验结果预期，LPS处理小鼠的器官（如脾脏、肺和腹腔渗出细胞）中IL-1RI、T1/ST2和MyD88的水平升高。有趣的是，虽然LPS处理后腹膜巨噬细胞中IL-1RII的表达受到抑制，与体外实验结果一致，但在肝脏、肺和脾脏等器官中观察到IL-1RII mRNA增加。5-氟尿嘧啶使小鼠中性粒细胞减少后，LPS的这种意外作用显著降低。因此，我们得出结论，LPS处理小鼠某些器官中IL-1RII的明显诱导是由于募集了表达高水平诱饵受体II的髓样细胞。因此，在体外和体内暴露于典型促炎信号LPS的单核吞噬细胞中，IL-1受体家族成员受到独立且不同的调节。
