Zhu X, Ertel W, Ayala A, Morrison M H, Perrin M M, Chaudry I H
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Immunology. 1993 Sep;80(1):122-6.
Although chloroquine administration in vivo following haemorrhage in mice decreases tumour necrosis factor-alpha (TNF-alpha) release by macrophage (M phi), the mechanism remains unknown. To study this, peritoneal M phi (pM phi) from unmanipulated, sham-operated and post-haemorrhage mice were isolated, treated with 0.13 mg/ml chloroquine for 2 hr, and then stimulated with lipopolysaccharide (LPS) for 48 hr. Pretreatment of pM phi from various groups of mice with chloroquine resulted in 75-90% inhibition of TNF-alpha release, determined by bioassay. Total RNA was isolated from pM phi and murine M phi-derived cell lines (P388D1 and RAW 264.7), stimulated with LPS for 0.5 or 1 hr, respectively, and Northern blot analysis for TNF-alpha mRNA performed. Chloroquine inhibited TNF-alpha mRNA expression without interfering with mRNA stability, suggesting that this agent reduces M phi TNF-alpha release by disrupting TNF-alpha gene transcription.
虽然在小鼠出血后进行体内氯喹给药可降低巨噬细胞（M phi）释放肿瘤坏死因子-α（TNF-α），但其机制尚不清楚。为研究此机制，从未处理、假手术和出血后的小鼠中分离出腹腔巨噬细胞（pM phi），用0.13 mg/ml氯喹处理2小时，然后用脂多糖（LPS）刺激48小时。用生物测定法测定，用氯喹预处理来自不同组小鼠的pM phi可导致TNF-α释放受到75 - 90%的抑制。分别用LPS刺激0.5或1小时后，从pM phi和小鼠M phi衍生的细胞系（P388D1和RAW 264.7）中分离总RNA，并进行TNF-α mRNA的Northern印迹分析。氯喹抑制TNF-α mRNA表达而不干扰mRNA稳定性，表明该药物通过破坏TNF-α基因转录来减少M phi TNF-α释放。
