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可抑制氧化应激诱导的细胞损伤/死亡。同时，表明HO-1的细胞保护作用严格依赖于酶活性的水平、位置和持续时间。特别是锚定依赖性细胞，如内皮细胞，对HO-1的过表达高度敏感，从而导致粘附分子的丢失和细胞凋亡。在循环单核细胞中，C16<bright> CCR2-亚群在体内产生HO-1，在保护内皮细胞功能中起关键作用。此外，这种特殊的单核细胞亚群在急性炎症性疾病中增加，表明它们通过防止过度的组织/器官损伤发挥重要的抗炎作用。肾小管上皮HO-1 mRNA表达增加与各种肾小球损伤的尿蛋白水平相关。然而，HO-1 mRNA的分布在不同发病机制的疾病中存在差异，表明HO-1 mRNA的表达模式反映了不同肾脏疾病组织损伤的不同机制。最近有研究表明，呼出空气中的一氧化碳反映了气道的炎症。原发性肺动脉高压患者肺组织中HO-1蛋白表达水平升高。主要产生HO-1的细胞为肺泡巨噬细胞、毛细血管腔内巨噬细胞、支气管壁内巨噬细胞和气道内巨噬细胞。这些结果表明，巨噬细胞通过在气道内产生不同水平的HO-1/CO来发挥抗炎作用。类固醇给药诱导了雄细胞表面血红蛋白/触珠蛋白复合物受体CD163的快速和显著增加。这些具有高CD163水平的单核细胞迅速摄取Hb/Hp复合物，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，而且对气道功能的维持也很重要。正在进行进一步调查以解决这些问题。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