Development of novel anti-inflammatory therapy through regulation of heme oxygenase-1 production by monocytes

血管损伤模型显示，HO-1抑制氧化应激诱导的细胞损伤/死亡。同时，提示HO-1的细胞保护作用与酶活性的水平、位置和持续时间密切相关。尤其是锚定依赖的细胞，如内皮细胞，对HO-1的过度表达高度敏感，HO-1导致黏附分子丢失和细胞凋亡。在循环单核细胞中，C16；CCR2-亚群被证明在体内产生HO-1，在保护内皮细胞的功能中起着关键作用。此外，这种特殊的单核细胞亚群在急性炎症性疾病期间增加，表明它们通过防止过度的组织/器官损害而发挥显著的抗炎作用。在各种肾小球损伤中，肾小管上皮细胞HO-1mRNA的表达增加与尿蛋白水平有关。而HO-1mR NA在…中的分布不同。HO-1mRNA的表达模式反映了不同肾脏疾病不同的组织损伤机制。最近研究表明，呼气空气中的CO反映了呼吸道的炎症。肺组织中HO-1蛋白表达水平升高。HO-1的主要产生细胞为肺泡巨噬细胞、毛细血管腔内巨噬细胞、支气管壁巨噬细胞和呼吸道巨噬细胞。这些结果表明，巨噬细胞通过在不同水平的气道内产生HO-1/CO而发挥抗炎作用。类固醇治疗导致人巨噬细胞表面血红蛋白/结合珠蛋白复合体受体CD163迅速而显著增加。这些高CD163水平的单核细胞迅速摄取Hb/Hp复合体，随后产生HO-1和IL-10。这些结果表明，单核细胞HO-1的产生不仅对血管内皮细胞的保护很重要，而且对维持呼吸道功能也是出乎意料的重要。目前正在进行进一步调查，以解决这些问题。较少

It was shown in a vascular injury model that HO-1 inhibits cell injury/death induced by oxidative stress. At the same time, it is suggested that the cytoprotective effect of HO-1 is strictly dependent on the level, location and duration of the enzyme activity. In particular, anchorage dependent cells, such as endothelial cells, are highly sensitive to overexpression of HO-1, which lead to the loss of adhesion molecules and apoptosis.Among circulating monocytes, C16<bright> CCR2- subpopulation is shown to produce HO-1 in vivo, playing critical role in protecting the functions of endothelial cells. Furthermore, this particular subpopulation of monocytes increases during acute inflammatory illnesses, suggesting that they play significant anti-inflammatory roles by preventing excessive tissue/organ damage.HO-1 mRNA expression within renal tubular epithelium increased in association with urinary protein levels in various glomerular injuries. However, the distribution of HO-1 mRNA varied amo … More ng illnesses of different pathogenesis, indicating that the pattern of HO-1 mRNA expression reflect distinct mechanisms of tissue injury in different kidney diseases.It has been shown recently that CO in expiratory air reflects inflammation of the airway. Increased levels of HO-1 protein expression were detected within in lung tissue of primary pulmonary hypertension. Major HO-1 producers were alveolar macrophages, and macrophages within capillary lumen, bronchial wall and airway. These results indicate that macrophages play anti-inflammatory roles by producing HO-1/CO within the airway at different levels.Steroid administration induced rapid and significant increase of CD163, receptors for hemoglobin/haptoglobin complex, on manocyte surfaces. These monocytes with high CD163 levels rapidly uptake Hb/Hp complex, and subsequently produced HO-1 and IL-10. These results indicate that monocyte HO-1 production is important not only for the protection of vascular endothelial cells, but unexpectedly for the maintenance of airway function. Further investigation is being performed to resolve these issues. Less