Rizzardini M, Terao M, Falciani F, Cantoni L
Heme and Hemoprotein Unit, Centro Daniela e Catullo Borgomainerio, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Biochem J. 1993 Mar 1;290 ( Pt 2)(Pt 2):343-7. doi: 10.1042/bj2900343.
Accumulation of the mRNA coding for haem oxygenase (HO, EC 1.14.99.3) was stimulated by treating mice with endotoxin (lipopolysaccharide, LPS; 20 micrograms/mouse intraperitoneally), suggesting that haem catabolism is a target of infection and inflammation in vivo. Therefore various cytokines, possible mediators for the biological responses to LPS, were administered intraperitoneally to mice, and the levels of HO mRNA were measured by Northern-blotting analysis using the rat HO cDNA as a probe [Shibahara, Müller, Taguchi and Yoshida (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7865-7869]. Marked induction of HO mRNA was observed 2 h after administration of interleukin 1 (IL-1) (34-fold) and tumour necrosis factor (19.5-fold) (5 micrograms/mouse), whereas interleukin 6 (6.2 micrograms/mouse) was much less active (3.5-fold) and interleukin 2 (25 micrograms/mouse) and interferon-gamma (3 micrograms/mouse) were ineffective. HO mRNA induced by the cytokines of LPS accumulated rapidly (maximum at 1-2 h after administration), preceding the elevation of HO enzymic activity. Treatment of mice with IL-1 stimulated the transcription of the HO gene by 4-fold, as assessed by in vitro nuclear-run-on assay. These results indicate that enzymic haem catabolism in the liver is a process inducible in vivo by inflammatory cytokines, which up-regulate HO synthesis at the transcriptional level. Increased removal of haem might be part of the protective mechanisms elicited by the acute-phase response, possibly to reduce the pro-oxidant state of the cell.
用内毒素（脂多糖，LPS；20微克/只小鼠，腹腔注射）处理小鼠，可刺激编码血红素加氧酶（HO，EC 1.14.99.3）的mRNA积累，这表明血红素分解代谢是体内感染和炎症的一个靶点。因此，将各种细胞因子（可能是对LPS生物学反应的介质）腹腔注射给小鼠，并使用大鼠HO cDNA作为探针，通过Northern印迹分析来测量HO mRNA的水平[Shibahara、Müller、Taguchi和Yoshida（1985年）《美国国家科学院院刊》82，7865 - 7869]。在注射白细胞介素1（IL - 1）（34倍）和肿瘤坏死因子（19.5倍）（5微克/只小鼠）2小时后，观察到HO mRNA有明显诱导，而白细胞介素6（6.2微克/只小鼠）活性低得多（3.5倍），白细胞介素2（25微克/只小鼠）和干扰素 - γ（3微克/只小鼠）则无作用。由LPS的细胞因子诱导的HO mRNA迅速积累（给药后1 - 2小时达到最大值），早于HO酶活性的升高。通过体外核转录分析评估，用IL - 1处理小鼠可使HO基因转录增加4倍。这些结果表明，肝脏中的酶促血红素分解代谢是炎症细胞因子在体内可诱导的一个过程，炎症细胞因子在转录水平上调HO的合成。血红素清除增加可能是急性期反应引发的保护机制的一部分，可能是为了降低细胞的促氧化状态。
