LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes

Angrisano, Tiziana; Pero, Raffaela; Peluso, Silvia; Keller, Simona; Sacchetti, Silvana; Bruni, Carmelo B.; Chiariotti, Lorenzo; Lembo, Francesca

doi:10.1186/1471-2180-10-172

Cited by 93 publications

(83 citation statements)

References 26 publications

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“…The change in gDNA methylation level found in this study was due to microbial infection and this is evident from previous studies which described the effect of lipopolysaccharide on DNA methylation [8][9][10].…”

Section: Discussionsupporting

confidence: 79%

Global DNA Methylation in Neonatal Sepsis

et al. 2014

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The index results showed that genomic DNA methylation varies significantly among newborns with sepsis (clinical, probable and culture positive) and without sepsis. Although the global DNA methylation was not a highly sensitive diagnostic method, this study reveals that DNA methylation might play a vital role in neonatal sepsis susceptibility. Identification of the specific differentially methylated genes might serve as a promising future diagnostic/prognostic marker for neonatal sepsis.

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Section: Discussionsupporting

confidence: 79%

Global DNA Methylation in Neonatal Sepsis

et al. 2014

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“…29 LPS-induced IL-8 activation in human intestinal epithelial cells was also reported to be accompanied by changes of specific histone H3 acetylation and methylation. 30 Histone deacetylation is mainly regulated by HDACs that control gene expression by means of removing acetyl groups from lysine residues in histone molecules and is closely related to epigenetic regulation of different genes. In our previous study, we demonstrated that LPS challenge causes deacetylation of H3 and H4 and inhibition of Thy-1 gene transcription in cultured mouse lung fibroblasts, indicating that LPS may silence Thy-1 gene through histone deacetylation at the Thy-1 gene promoter region.…”

Section: Discussionmentioning

confidence: 99%

HDAC is essential for epigenetic regulation of Thy-1 gene expression during LPS/TLR4-mediated proliferation of lung fibroblasts

Xing

Nie

et al. 2015

Laboratory Investigation

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Lipopolysaccharide (LPS)-induced proliferation of lung fibroblasts is closely correlated with loss of gene expression of thymocyte differentiation antigen-1 (Thy-1), accompanied with deacetylation of histones H3 and H4 at the Thy-1 gene promoter region; however, the mechanism remains enigmatic. We report here that LPS downregulates Thy-1 gene expression by activating histone deacetylases (HDACs) via Toll-like receptor 4 (TLR4) signaling. Treatment of primary cultured mouse lung fibroblasts with LPS resulted in significant upregulation of TLR4 and enhanced cell proliferation that was abolished by silencing TLR4 with lentivirus-delivered TLR4 shRNA. Interestingly, LPS increased the mRNA and protein levels of HDAC-4, -5, and -7, an effect that was abrogated by HDAC inhibitor trichostatin A (TSA) or TLR4-shRNA-lentivirus. Consistent with these findings, Ace-H3 and Ace-H4 were decreased by LPS that was prevented by TSA. Most importantly, chromosome immunoprecipitation (ChIP) analysis demonstrated that LPS decreased the association of Ace-H4 at the Thy-1 promoter region that was efficiently restored by pretreatment with TSA. Accordingly, LPS decreased the mRNA and protein levels of Thy-1 that was inhibited by TSA. Furthermore, silencing the Thy-1 gene by lentivirus-delivered Thy-1 shRNA could promote lung fibroblast proliferation, even in the absence of LPS. Conversely, overexpressing Thy-1 gene could inhibit lung fibroblast proliferation and reduce LPS-induced lung fibroblast proliferation. Our data suggest that LPS upregulates and activates HDACs through TLR4, resulting in deacetylation of histones H3 and H4 at the Thy-1 gene promoter that may contribute to Thy-1 gene silencing and lung fibroblast proliferation. Pulmonary fibrosis is characterized by aberrant proliferation and activation of lung fibroblasts. 1,2 The phenotypic transition of lung fibroblasts during the process of pulmonary fibrosis can be stimulated by various pathological conditions, including lipopolysaccharide (LPS), a component of bacteria membranes and an important player during the development of pulmonary fibrosis. 3,4 LPS-induced proliferation of lung fibroblast is associated with the silencing of thymocyte differentiation antigen-1 (Thy-1) and deacetylation of histones H3 and H4 at the Thy-1 gene promoter; 5,6 however, the mechanism by which LPS promotes the deacetylation of histones H3 and H4 leading to downregulation of Thy-1 gene expression is largely unknown.Thy-1 is a cell surface glycoprotein that is present in normal lung fibroblasts but absent from the fibroblastic foci of idiopathic pulmonary fibrosis (IPF). 7 Heterogeneous surface expression of Thy-1 in fibroblasts results in the specialization of fibroblast, including Thy-1 (+) and Thy-1 (− ) subsets. Hagood et al 5,8,9 reported that lack of Thy-1 expression on lung fibroblasts contributed to IPF. Recently, it was found that epigenetic mechanisms, such as promoter hypermethylation and histone modification, play an important role in Thy-1 gene silencing in lung fibroblasts. 6,7 Our...

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“…One recent study indicated that a change in H3S10 phosphorylation status at IL-6 gene promoter is related to Hp infection through NFkB/ERK/p38 pathway [26]. We have recently demonstrated that chromatin and DNA methylation modifications accompany Hp-induced Cox-2 activation in gastric epithelial cells [27] and LPS-induced IL-8 activation in human intestinal epithelial cells [28]. In this work, we hypothesized that Hp infection may have a direct impact on epigenetic status of iNOS gene in gastric cells and that the Hp-induced iNOS activation may be mediated by histone modifications at iNOS gene regulatory regions.…”

Section: Introductionmentioning

confidence: 95%

Helicobacter pylori regulates iNOS promoter by histone modifications in human gastric epithelial cells

Angrisano

Lembo

Peluso

et al. 2012

Med Microbiol Immunol

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Inducible nitric oxide synthase (iNOS) expression is altered in gastrointestinal diseases. Helicobacter pylori (Hp) infection may have a critical role in iNOS disregulation. We undertook this study to investigate possible chromatin changes occurring early during iNOS gene activation as a direct consequence of Hp-gastric cells interaction. We show that Hp infection is followed by different expression and chromatin modifications in gastric cells including (1) activation of iNOS gene expression, (2) chromatin changes at iNOS promoter including decreased H3K9 methylation and increased H3 acetylation and H3K4 methylation levels, (3) selective release of methyl-CpG-binding protein 2 from the iNOS promoter. Moreover, we show that Hp-induced activation of iNOS is delayed, but not eliminated, by the treatment with LSD1 inhibitors. Our data suggest a role for specific chromatin-based mechanisms in the control of human iNOS gene expression upon Hp exposure.

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LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes

Cited by 93 publications

References 26 publications

Global DNA Methylation in Neonatal Sepsis

Global DNA Methylation in Neonatal Sepsis

HDAC is essential for epigenetic regulation of Thy-1 gene expression during LPS/TLR4-mediated proliferation of lung fibroblasts

Helicobacter pylori regulates iNOS promoter by histone modifications in human gastric epithelial cells

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