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 4Downregulation of
IL-10 transcript and protein levels by TSA and SAHA. (
a) TSA (300–500 ng/ml) decreases the levels of
IL-10 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 LPS (100 ng/ml) plus IFN-γ (100 IU/ml) for 6 or 18 hours.
IL-10 mRNA levels relative to
GAPDH are shown. (
c) Based on densitometric scanning of the gel in
b, this graph depicts the fold change of
IL-10 mRNA in cells cultured as described above. A representative of three independent experiments is shown. (
d) Splenocytes from 10-week-old mice were cultured for 72 hours in the presence of vehicle, LPS, LPS plus TSA, LPS plus SAHA, ConA, ConA plus TSA, ConA plus SAHA, LPS plus IFN-γ, LPS plus IFN-γ plus TSA, or LPS plus IFN-γ plus SAHA. The concentrations of TSA and SAHA were 300 ng/ml and 10 μM, respectively. This graph depicts the amount of IL-10 protein secretion. The bar represents the mean ± SEM of three independent experiments.
