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 2Downregulation of
IL-12 transcript and protein levels by TSA and SAHA. (
a) Increasing concentrations of TSA (0–500 ng/ml) progressively decrease levels of
IL-12p40 and
IL-12p35 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-12p40 and
IL-12p35 mRNA levels relative to
GAPDH are shown. (
c and
d) Based on densitometric scanning of the gel in
b, these graphs depict the fold change of
IL-12p40 (
c) and
IL-12p35 (
d) mRNA in cells cultured as described above. A representative of three independent experiments is shown. (
e) Splenocytes from 10-week-old mice were cultured in the presence of vehicle, TSA, LPS plus IFN-γ, LPS plus IFN-γ plus TSA, LPS plus IFN-γ plus SAHA, or SAHA for 24 hours. The concentrations of TSA and SAHA were 300 ng/ml and 10 μM, respectively. This graph depicts the amount of IL-12p40 protein secretion. The bar represents the mean ± SEM of three independent experiments.
