71 3 Responses of alveolar-like macrophages to lysine deacetylase inhibition cytokine (42). While treatment with LPS did not induce TGFβ expression (Figure 3B), pretreatment with KDAC1/2/3 inhibitor MS275, but not with KDAC3 inhibitor RGFP966, resulted in significantly higher TGFβ expression compared to LPS treatment alone, further supporting an anti-inflammatory effect of MS275. Figure 2: Effects of LPS and/or KDAC inhibitors MS275 or RGFP966 on TNF-α and IL-10 excretion in culture supernatant of alveolar-like macrophages. Alveolar-like macrophages were incubated with 1 ug/ml KDAC1/2/3 inhibitor MS275 (KDAC1+2+3i), KDAC3 inhibitor RGFP966 (KDAC3i), or vehicle for 16 h and then stimulated with 10 ng/ml LPS or vehicle for 4 h. (A) Effects on TNFα excretion. Colored dots indicate the different independent replicates. (B) Effects on IL-10 excretion. Colored dots indicate the different independent replicates. A Wilcoxon test was used to compare control versus LPS stimulation. Groups stimulated with or without KDAC inhibitors were compared using a Friedman test with a Dunn’s correction for multiple testing (n=5). P<0.05 was considered significant. Taken together, these results confirm previous observations in monocyte-derived macrophages (20,21) and show that in alveolar-like macrophages, KDAC3 inhibition blocks pro-inflammatory responses and stimulates anti-inflammatory ones, while the effects of KDAC1/3 inhibition are mixed.
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