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. Author manuscript; available in PMC: 2011 Jul 1.
Published in final edited form as: Nat Immunol. 2010 Dec 5;12(1):29–36. doi: 10.1038/ni.1968

Figure 4. SETD6 attenuates RelA-driven inflammatory responses.

Figure 4

(a) Negative correlation between SETD6 mRNA expression and NF-kB-linked inflammatory diseases. Left: SETD6 expression level was lower (p = 0.00036, two-tailed t test) in rheumatoid arthritis (RA) patients (n = 8) compared to healthy controls (n = 15). Expression level is shown as the normalized log2 ratio of the sample compared to a common reference. Right: SETD6 expression was lower (p = 0.0015, two-tailed t test) in septic shock patients (n=30) compared to healthy controls (n = 15). See Methods for data sources and detailed filtering criteria. (b) SETD6 depletion enhanced TNF-induced cytokine secretion in THP-1 monocytic cells. THP-1 cells were transfected with control (ct.) or SETD6 siRNA ± TNF (20 ng/ml). Secretion of indicated cytokines into the culture supernatant was measured by ELISA. (c) Kinetics of SETD6-mediated inhibition of RelA target gene expression in response to TNF in mBMDM cells. Levels of IL1a and TNF mRNA measured by RT PCR at the indicated time points after TNF treatment of mBMDM cells transfected with control or SETD6 siRNA. (d) SETD6 depletion in mBMDM cells enhanced TNF-induced secretion of a large number of RelA-regulated cytokines. Primary mBMDM cells were treated as in (c) and culture supernatants were assayed for the indicated cytokines by multiplex ELISA at the 2-hr time point. y-axis: (SETD6 siRNA cytokine level/control siRNA − 1) × 100. Representative data of two independent experiments is shown. (e) siRNA-mediated depletion of SETD6 in primary human monocyte-derived dendritic cells (hMDDC). hMDDC from three individual donors were transfected with a control (ct.) siRNA or two independent SETD6 siRNAs, and the amount of SETD6 mRNA were measured by RT PCR analysis. (f) SETD6 depletion enhanced LPS-induced TNF and IL6 cytokine secretion in primary hMDDC. (Left) Average fold change of the indicated cytokines secreted from hMDDCs as in (e) and measured at 6 hrs and 24 hrs. (Right) Cytokine secretion (ng/ml) of hMDDCs isolated from an individual human donor 24 h after treatment with 10 or 100 ng/ml of LPS and transfected with the indicated siRNAs. Error bars in (b, c, e, f) indicate ± s.e.m. from at least three independent experiments.