Abstract
Backgrounds: It has been reported that anti-neutrophil cytoplasmic antibodies (ANCA) activate neutrophils result in induction of glomerulonephritis in Wegener's Granulomatosis (WG) by released hydrogen peroxide.
Histone deacetylase (HDAC) deacetylates histone and deacetylation of histone associates with gene repression.
In this study, we investigated whether HDAC2 function decreased in WG patients, and effect of oxidative stress on function of HDAC2.
Patients and methods: A549 cells (lung epithelial cells) were stimulated by H2O2 to induce oxidative stress and expression of HDAC 2 and HDAC2 activity were measured.
Six patients of WG diagnosed according to American College of Rheumatology criteria were examined.
Fresh PBMCs were isolated from heparinized blood and then whole cell protein was prepared. Target proteins were detected by Western blot analysis. We also measured HDAC 2 activity on patients.
Results: Treatment of A549 cells with H2O2 did not suppress expression of HDAC2. However, treatment of H2O2 significantly decreased total HDAC2 activity (p < 0.05).
We found that HDAC 2 activity was significantly decreased in WG patients compared with healthy subjects (HS), 75.5±7.4 Arbitral Units at HS, 35.2±12.3 AU at WG (p < 0.05). Furthermore, we found negative correlation between HDAC 2 activity and titer of c-reactive protein and titer of PR3-ANCA.
Discussion: These results suggest that function of HDAC 2 is reduced in WG and that this reduction affects inflammation and vasculitis of WG. Oxidative stress may worsen the disease via reduction of HDAC2 function. Thus, HDAC2 may serve therapeutic targets by modulating the function, which eventually regulates the development of WG.
- © 2011 ERS