Suppression of lipopolysaccharide- and tumour necrosis factor-α-induced interleukin (IL)-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation

Abstract

SummaryThere is accumulating evidence that the transrepressional effect of glucocorticoids in down-regulating proinflammatory gene expression might be regulated by an action on histone acetylation. To investigate this, we studied the effect of two glucocorticoids (dexamethasone and triamcinolone acetonide) on reducing lipopolysaccharide (

Epigenetic Regulation of Tumor Necrosis Factor α (TNFα) Release in Human Macrophages by HIV-1 Single-stranded RNA (ssRNA) Is Dependent on TLR8 Signaling

“…In our study, we showed in human macrophages that chromatin remodeling occurs as a consequence of HIV-1 ssRNA-induced TLR8 activation, leading to TNF␣ release. These results are consistent with those in peripheral blood mononuclear cells and mouse macrophages in which dependence of TLR4-induced increase in pro-inflammatory cytokine release is dependent on chromatin remodeling (39). In addition to the modifications described by Tsaprouni et al (39), we found that histone 3 lysine 4 (H3K4me3) methylation was also markedly increased, with concomitant decrease in histone 3 lysine 27 (H3K27me3) methylation.…”

Repression of TNF-α-induced IL-8 expression by the glucocorticoid receptor-β involves inhibition of histone H4 acetylation

“…It is known that suppression of TNF-α-induced IL-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation (Tsaprouni et al, 2007). As shown in Figure 6, IPs with antibody against acetylated histone H4 revealed a marked enrichment of the IL-8 promoter DNA after TNF-α treatment.…”

“…Chromatin remodeling following histone acetylation at the specific gene promoter site is a major transcriptional regulatory mechanism that allows transcription factors to bind to specific gene promoters, initiating gene transcription. Tsaprouni et al (2007) reported that the ability of TNF-α to induce IL-8 expression in monocyte and T cell lines is regulated by changes in histone acetylation. Our data show that overexpression of GRβ did not show any negative effect on the glucocorticoid-induced transrepression, expression of mRNA, and secretion of IL-8, rather it looked like that GRβ had its own weak transrepressive activity, while it caused inhibition of glucocorticoid-induced transactivation.…”

“…Glucocorticoid-induced suppression of inflammatory cytokines is important in the regulation of many inflammatory diseases, and suppression of TNF-α-induced IL-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation (Tsaprouni et al, 2007). Recent in vitro data verified that GRα and GRβ act in a similar manner on IL-5 and IL-13 promoters, serving to repress transcription via recruitment of histone deacetylase (HDAC) and GRβ does not act as a dominantnegative inhibitor of GRα in this transrepression (Kelly et al, 2008).…”

A veleszületett immunitás szabályozásának vizsgálata in vitro és in vivo rendszerekben

“…Ez is jól mutatja, hogy a hiszton acetiláció a génexpressziós mintázatokat a konkrét stimulus alapján szabályozza (Schmeck, 2005). Így, például LPS esetén is megfigyelhető a CXCL8 expressziójának növekedése, ami a H4 hiszton acetilációs szintjének emelkedésével jár együtt (Tsaprouni, 2007).…”