2005 Fiscal Year Final Research Report Summary
Development of novel anti-inflammatory therapy through regulation of heme oxygenase-1 production by monocytes
| Project/Area Number |
16591014
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
YACHIE Akihiro Kanazawa University, Graduate School of Medical Science, Professor, 医学系研究科, 教授 (40210281)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | heme oxygenase / inflammation / monocyte / oxidized LDL / cell injury / cytokine |
|---|
| Research Abstract |
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
|
