Lee C G, Demarquoy J, Jackson M J, O'Brien W E
Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
J Immunol. 1994 Jun 15;152(12):5758-67.
Murine macrophages respond to endotoxins by inducing a vast array of genes that play a major role in the host's response to infection and tumor growth. We have isolated and characterized a 1.8-kb cDNA, designated IRG2, from a cDNA library prepared from RNA isolated from the murine cell line, RAW 264.7, after bacterial LPS stimulation. The cDNA encodes a protein of 47 kDa that is the murine homologue of a small family of proteins described from IFN-induced human cells. The IRG2 message does not appear until 3 h after LPS exposure and its induction is dependent on new protein synthesis. IRG2 induction by LPS is slightly inhibited by the anti-inflammatory steroid, dexamethasone. Increasing cytosolic cAMP with either forskolin, dibutyryl cAMP, or 8-(4-chlorophenylthio)-cAMP caused marked inhibition of the LPS induction of IRG2. In contrast, activation of PKC with phorbol ester potentiated the LPS response. Removing extracellular Ca2+ with EGTA inhibited IRG2 induction; increasing intracellular calcium with the calcium ionophore A23187 led to enhanced levels of the IRG2 transcript. These data suggest that the induction of IRG2 occurs via a PKC pathway.
小鼠巨噬细胞通过诱导大量基因来响应内毒素，这些基因在宿主对感染和肿瘤生长的反应中起主要作用。我们从经细菌脂多糖（LPS）刺激后的小鼠细胞系RAW 264.7中分离出的RNA制备的cDNA文库中，分离并鉴定了一个1.8 kb的cDNA，命名为IRG2。该cDNA编码一种47 kDa的蛋白质，它是在IFN诱导的人类细胞中描述的一小类蛋白质的小鼠同源物。IRG2信息直到LPS暴露后3小时才出现，其诱导依赖于新的蛋白质合成。LPS对IRG2的诱导受到抗炎类固醇地塞米松的轻微抑制。用福司可林、二丁酰cAMP或8-（4-氯苯基硫代）-cAMP增加胞质cAMP会显著抑制LPS对IRG2的诱导。相反，用佛波酯激活PKC会增强LPS反应。用EGTA去除细胞外Ca2+会抑制IRG2的诱导；用钙离子载体A23187增加细胞内钙会导致IRG2转录本水平升高。这些数据表明，IRG2的诱导是通过PKC途径发生的。
