HDAC1 and HDAC2 regulate anti‐inflammatory effects of anesthetic isoflurane in human monocytes

Guo, Xinying; Deng, Jie; Zheng, Bin; Líu, Hao; Zhang, Yuehong; Ying, Yanlu; Jia, Jie; Ruan, Xiuxiu

doi:10.1111/imcb.12318

Cited by 18 publications

(10 citation statements)

References 37 publications

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“…Loss of HDAC1 could prolong nuclear IL-1β-triggered phosphorylation of nuclear factor kappa-B and control the levels of IL-1β-dependent inflammatory genes in intestinal epithelial cells 30 . This role of HDAC1 in inflammation has also been elaborated in another study that HDAC1 inhibition blocks the suppression of proinflammatory responses 31 . HDAC1, a histone deacetylase, was found to reduce H3K27ac in the NEP promoter and hence downregulate NEP expression.…”

Section: Discussionmentioning

confidence: 70%

ATF4-mediated histone deacetylase HDAC1 promotes the progression of acute pancreatitis

Deng

Miao

et al. 2021

Cell Death Dis

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Acute pancreatitis (AP), an acute inflammatory process, can be difficult to diagnose. Activating transcription factor 4 (ATF4) has been reported to participate in the pathogenesis of AP. Additionally, histone deacetylases (HDACs) are shown to be closely related to the development of a variety of diseases, including inflammation disease. In our study, we tried to highlight the role of ATF4 in AP through regulation of HDAC1. Firstly, we validated the effect of ATF4 on pancreatic acinar cell proliferation, apoptosis, and inflammation through in vitro experiments on cellular models of caerulein-induced AP. Next, we examined the correlation between ATF4 and HDAC1, and between HDAC1 with neutral endopeptidase (NEP) and kruppel-like factor 4 (KLF4). Finally, the regulatory role of ATF4 in AP was further assessed by determination of pathological conditions, biochemical indicators and inflammation through in vivo experiments on caerulein-induced AP mouse models. After AP induction, highly expressed ATF4 was observed, and silencing ATF4 could promote pancreatic acinar cell proliferation and inhibit apoptosis. ATF4 could bind to the HDAC1 promoter and upregulate its expression in AP. Moreover, HDAC1 could increase KLF4 expression by inhibiting NEP expression. Functionally, silencing ATF4 could suppress AP through regulation of NEP-mediated KLF4 via downregulation of HDAC1. Above all, our study uncovered the promotive role of ATF4 in AP through upregulation of HDAC1.

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Section: Discussionmentioning

confidence: 70%

ATF4-mediated histone deacetylase HDAC1 promotes the progression of acute pancreatitis

Deng

Miao

et al. 2021

Cell Death Dis

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“…Erythromycin may increase the activity of HDAC2 via inhibiting the PI3K/Akt pathway and reducing the release of inflammatory factors, such as IL-8, thereby increasing the anti-inflammatory activity of budesonide (13). In human THP-1 cells stimulated with lipopolysaccharide and primary human peripheral blood mononuclear cells, pretreatment with the HDAC inhibitor trichostatin A or gene silencing of HDAC1 and HDAC2 inhibited the antiinflammatory effects of isoflurane and increased the expression of TNF-α, IL-8 and interleukin-1β (51). These studies indicated that increasing the expression/activity of HDAC2 reduces the release of the inflammatory factor IL-8 and enhances the anti-inflammatory effect, while inhibiting the expression/activity of HDAC2 increases the release of the inflammatory factor IL-8 and aggravates the inflammatory response (13,50,51).…”

Section: Discussionmentioning

confidence: 99%

“…In human THP-1 cells stimulated with lipopolysaccharide and primary human peripheral blood mononuclear cells, pretreatment with the HDAC inhibitor trichostatin A or gene silencing of HDAC1 and HDAC2 inhibited the antiinflammatory effects of isoflurane and increased the expression of TNF-α, IL-8 and interleukin-1β (51). These studies indicated that increasing the expression/activity of HDAC2 reduces the release of the inflammatory factor IL-8 and enhances the anti-inflammatory effect, while inhibiting the expression/activity of HDAC2 increases the release of the inflammatory factor IL-8 and aggravates the inflammatory response (13,50,51). A clinical study revealed that mechanical damage, which was triggered via tracheal intubation induced an increased expression of TGF-β, VEGF, and basic fibroblast growth factor, which resulted in enhanced expression of collagen type I and III, tracheal granulation hyperplasia and tracheal stenosis (52).…”

Section: Discussionmentioning

confidence: 99%

Expression of histone deacetylase 2 in tracheal stenosis models and its relationship with tracheal granulation tissue proliferation

et al. 2021

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The current treatments for benign tracheal stenosis are inefficient. The present study examined the expression of histone deacetylase 2 (HDAC2) in different tracheal stenosis models and explored its association with the proliferation of tracheal granulation tissue and its ability to constitute a potential therapy for tracheal stenosis. Animal tracheal stenosis models were established, as indicated by hematoxylin and eosin (H&E) staining. A total of 24 New Zealand White rabbits were randomly divided into control, erythromycin, budesonide and vorinostat groups. Stenotic tracheal tissues were collected on day 11 after drug administration for 10 days. The degree of tracheal stenosis in each group was calculated, and pathological alterations were observed using H&E staining. The mRNA expression of HDAC2, interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) was examined via reverse transcription-quantitative PCR. The protein expression of HDAC2 was examined via immunofluorescence, while the expression of type I and type III collagen was assessed using immunohistochemistry. The results of the present study demonstrated that tracheal epithelial hyperplasia in the erythromycin group was improved, the degree of hyperplasia being the lowest among all groups, and tracheal stenosis was reduced compared with the control group. In the vorinostat group, tracheal epithelial tissue hyperplasia was aggravated and stenosis was increased. The HDAC2 mRNA and protein levels were increased and decreased in the erythromycin and vorinostat groups, respectively. In contrast, the IL-8 mRNA expression levels were decreased and increased in the erythromycin and vorinostat groups, respectively. TGF-β1, VEGF, type I and type III collagen expression was decreased in the erythromycin group, while TGF-β1, VEGF and type III collagen expression was increased in the vorinostat group. Compared with the control, the budesonide group did not exhibit any alterations in all of the indicators examined, including TGF-β1, VEGF, IL-8, HDAC2 and collagen. Erythromycin treatment upregulated the expression of HDAC2, inhibited the inflammatory responses and reduced the proliferation of tracheal granulation tissue. In contrast, vorinostat treatment downregulated HDAC2 expression, promoted the inflammatory responses and increased the proliferation of tracheal granulation tissue. These results suggest that regulating HDAC2 may be used as a potential treatment for benign tracheal stenosis.

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“…Coimmunoprecipitation assays were performed with a co-immunoprecipitation kit (Pierce) according to the manufacturer's instructions, as previously described [28]. In brief, the spinal dorsal horn tissues were quickly minced and homogenized in lysis buffer.…”

Section: Coimmunoprecipitation Assays (Co-ip)mentioning

confidence: 99%

Downregulation of Metallothionein-2 Contributes to Oxaliplatin-induced Neuropathic Pain

Huang

Deng

et al. 2020

Preprint

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Background We previously reported a correlation between small doses of oxaliplatin penetrating onto the spinal cord and acute pain after chemotherapy. Here we propose that MT2 within the spinal dorsal horns participates the development of oxaliplatin-induced neuropathic pain and may be a pharmacological target for the prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN). Methods The rat model of CIPN was established by a 5 consecutive injection of oxaliplatin (0.4 mg/ 100 g/ day). Genetic restoration or inhibition of neuron-specific metallothionein-2 was implemented 21 days before oxaliplatin treatment. Mechanical allodynia and locomotor activity were assayed. Cell-specific expression of metallothionein-2, the mRNA levels of pro-inflammatory cytokines, nuclear translocation of NF-κB, the protein levels of expression of IκB-α, and interaction between IκB-α and P65 were evaluated in the spinal dorsal horns. Also, in vitro interaction of sequentially deleted IκB-α promoter with metallothionein-2 was used to assess the signal transduction mechanism. Results We found that oxaliplatin induced downregulation of metallothionein-2 in rat spinal cord neurons. By contrast, genetic restoration of metallothionein-2 in the spinal dorsal horn neuron blocked and reversed neuropathic pain in oxaliplatin-treated rats of both sexes, whereas genetic inhibition of metallothionein-2 triggered neuropathic pain in normal rats. No locomotor impairment was observed after the genetic alterations of metallothionein-2. At the molecular level, metallothionein-2 modulated oxaliplatin-induced neuroinflammation, activation of NF-κB, and transcriptional expression of IκB-α promoter, and these processes could be blocked by genetic restoration of metallothionein-2 in the spinal dorsal horn neurons. Conclusions Metallothionein-2 is a potential target for the prevention and treatment of CIPN. A reduction of NF-κB activation and inflammatory responses by enhancing the transcription of IκB-α promoter is proposed in the mechanism.

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HDAC1 and HDAC2 regulate anti‐inflammatory effects of anesthetic isoflurane in human monocytes

Cited by 18 publications

References 37 publications

ATF4-mediated histone deacetylase HDAC1 promotes the progression of acute pancreatitis

ATF4-mediated histone deacetylase HDAC1 promotes the progression of acute pancreatitis

Expression of histone deacetylase 2 in tracheal stenosis models and its relationship with tracheal granulation tissue proliferation

Downregulation of Metallothionein-2 Contributes to Oxaliplatin-induced Neuropathic Pain

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