Dysregulation of histone deacetylase and histone acetyltransferase in development of Wegener's granulomatosis.
OBJECTIVE
We investigated the function of the decreases in histone deacetylase (HDAC) and histone acetyltransferase (HAT) in Wegener's granulomatosis (WG) patients compared with healthy subjects.


METHODS
Seven patients with WG, diagnosed according to the American College of Rheumatology criteria, were examined. Fresh peripheral blood mononuclear cells were isolated from the WG patients and healthy subjects, and then whole-cell proteins were prepared. We measured the total HDAC and HAT activity in peripheral blood mononuclear cells from WG patients. The HDAC2 expression was analyzed by Western blot.


RESULTS
We found that total HDAC activity was significantly decreased in WG patients compared to that in healthy subjects (p < 0.05). Furthermore, we found a negative correlation between total HDAC activity and C-reactive protein titer. Total HAT activity was significantly increased in WG patients.


CONCLUSIONS
These results demonstrated reduced HDAC activity and an increase in HAT activity in WG. These were associated with concomitant induction of WG-related inflammation. Thus, dysregulation of HDAC and HAT may contribute to the disease pathogenesis of WG.
Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Dai
D
Takagi
Yuji
Y
Nakamaru
Masanobu
M
Suzuki
Satoshi
S
Fukuda
D000107:Acetylation; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000503:physiopathology*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
D019268:Antibodies, Antineutrophil Cytoplasmic; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases