Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse
J. Clin. Invest. Nilamadhab Mishra, et al. 111:539 doi:10.1172/JCI16153 [
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Figure 1Downregulation of
IFN-γ transcript and protein levels by TSA and SAHA. (
a) TSA (300–500 ng/ml) decreases the level of
IFN-γ mRNA relative to
GAPDH mRNA in splenocytes from 24-week-old MRL-
lpr/lpr mice. (
b) Splenocytes from 10-week-old MRL-
lpr/lpr mice were incubated in the absence or presence of 300 ng/ml TSA or 10 μM SAHA for 18 hours. Splenocytes were then stimulated with ConA (10 μg/ml) for 18 hours. In lanes 3 and 5, TSA or SAHA was added at the same time as ConA and cultured for 18 hours.
IFN-γ mRNA levels relative to
GAPDH are shown. (
c) Based on densitometric scanning of the gel in
b, this graph depicts the fold change of
IFN-γ mRNA in cells cultured as described above. A representative of three independent experiments is shown. (
d) Splenocytes from 10-week-old mice were cultured in the presence of vehicle, LPS, LPS plus TSA, LPS plus SAHA, ConA, ConA plus TSA, or ConA plus SAHA for 72 hours. The concentrations of TSA and SAHA were 300 ng/ml and 10 μM, respectively. This graph depicts the amount of IFN-γ protein secretion. The bar represents the mean ± SEM of three independent experiments.
