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Gun D. Kim

Bio: Gun D. Kim is an academic researcher from Georgetown University Medical Center. The author has contributed to research in topics: Inflammation & Medicine. The author has an hindex of 1, co-authored 1 publications receiving 111 citations.
Topics: Inflammation, Medicine, Chemokine, COPD, HDAC10

Papers
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Journal ArticleDOI
TL;DR: Binding and immunoprecipitation assays have shown that ATM interacts with the histone deacetylase HDAC1 both in vitro and in vivo, and that the extent of this association is increased after exposure of MRC5CV1 human fibroblasts to ionizing radiation.

116 citations

Journal ArticleDOI
TL;DR: The mitigation effect of AGE on lung inflammation via inhibition of MAPK and NF-κB pathways is demonstrated, suggesting that AGE may be instrumental in improving respiratory and lung health.
Abstract: Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease (COPD), and continuous CS exposure causes lung inflammation and deterioration. To investigate the protective effects of Artemisia gmelinii against lung inflammation in this study, cigarette smoke extract (CSE)/lipopolysaccharide (LPS)-treated alveolar macrophages (AMs) and mice stimulated with CSE/porcine pancreas elastase (PPE) were used. Artemisia gmelinii ethanol extract (AGE) was effective in decreasing the levels of cytokines, chemokine, inducible nitric oxide synthase, and cyclooxygenase-2 by inhibiting mitogen-activated protein (MAP) kinases/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in AMs. Additionally, oral administration of AGE suppressed inflammatory cells’ infiltration and secretion of inflammatory cytokines, chemokines, matrix metallopeptidase 9, and neutrophil extracellular traps in bronchoalveolar lavage fluid from the COPD model. Moreover, the obstruction of small airways, the destruction of the lung parenchyma, and expression of IL-6, TNF-α, IL-1β, and MIP-2 were suppressed by inhibiting NF-κB activation in the lung tissues of the AGE group. These effects are associated with scopolin, chlorogenic acid, hyperoside, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid, which are the main components of AGE. These data demonstrate the mitigation effect of AGE on lung inflammation via inhibition of MAPK and NF-κB pathways, suggesting that AGE may be instrumental in improving respiratory and lung health.

5 citations

Journal ArticleDOI
TL;DR: It is suggested that the CLE administration be the effective approach for treating or preventing chronic pulmonary diseases such as COPD induced by CS.
Abstract: Cigarette smoke (CS) is the major factor in the development of chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. Furthermore, although Camellia sinensis (CN) has been known as an anti-inflammatory material, the effect of CN has not yet been known on pulmonary inflammation in COPD. Thus, we investigated the protective effects of Camellia sinensis L. extract (CLE) against pulmonary inflammation in porcine pancreas elastase (PPE) and a cigarette smoke extract (CSE)-induced COPD mouse model. Oral administration of CLE suppressed the symptoms such as infiltration of immune cells, cytokines/chemokines secretion, mucus hypersecretion, and injuries of the lung parenchyma. Increased inflammatory responses in COPD are mediated by various immune cells such as airway epithelial cells, neutrophils, and alveolar macrophages. Thus, we investigated the effect and mechanisms of CLE in H292, HL-60, and MH-S cells. The CLE inhibited the expression of IL-6, IL-8, MUC5AC and MUC5B on CSE/LPS-stimulated H292 cells and also suppressed the formation of neutrophil extracellular traps and secretion of neutrophil elastase by inhibiting reactive oxygen species in PMA-induced HL-60 cells. In particular, the CLE suppressed the release of cytokines and chemokines caused by activating the nuclear factor kappa-light-chain-enhancer of activated B via the activation of nuclear factor erythroid-2-related factor 2 and the heme oxygenase-1 pathway in CSE/LPS-stimulated MH-S cells. Therefore, we suggest that the CLE administration be the effective approach for treating or preventing chronic pulmonary diseases such as COPD induced by CS.

2 citations

Journal ArticleDOI
TL;DR: In this article , the authors investigated the effect of fermented Lillium longiflorum thunb (LLT) bulb extract fermented with Lactobacillus acidophilus 803 in COPD mouse models induced by CSE and porcine pancreas elastase (PPE).
Abstract: Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is caused by repeated exposure to harmful matter, such as cigarette smoke. Although Lilium longiflorum Thunb (LLT) has anti-inflammatory effects, there is no report on the fermented LLT bulb extract regulating lung inflammation in COPD. Thus, we investigated the protective effect of LLT bulb extract fermented with Lactobacillus acidophilus 803 in COPD mouse models induced by cigarette smoke extract (CSE) and porcine pancreas elastase (PPE). Oral administration of the fermented product (LS803) suppressed the production of inflammatory mediators and the infiltration of immune cells involving neutrophils and macrophages, resulting in protective effects against lung damage. In addition, LS803 inhibited CSE- and LPS-induced IL-6 and IL-8 production in airway epithelial H292 cells as well as suppressed PMA-induced formation of neutrophil extracellular traps in HL-60 cells. In particular, LS803 significantly repressed the elevated IL-6 and MIP-2 production after CSE and LPS stimulation by suppressing the activity of the nuclear factor kappa-light-chain-enhancer of activated B (NFκB) in mouse peritoneal macrophages. Therefore, our results suggest that the fermented product LS803 is effective in preventing and alleviating lung inflammation.

Cited by
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Journal ArticleDOI
TL;DR: Recent advances in the understanding of the molecular events that underlie the anticancer effects of HDAC inhibitors are summarized and how such information could be used in optimizing the development and application of these agents in the clinic, either as monotherapies or in combination with other anticancer drugs are discussed.
Abstract: Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. In addition, the activity of non-histone proteins can be regulated through HDAC-mediated hypo-acetylation. In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. However, such studies have also indicated that the effects of HDAC inhibitors could be considerably broader and more complicated than originally understood. Here we summarize recent advances in the understanding of the molecular events that underlie the anticancer effects of HDAC inhibitors, and discuss how such information could be used in optimizing the development and application of these agents in the clinic, either as monotherapies or in combination with other anticancer drugs.

2,777 citations

Journal ArticleDOI
TL;DR: The remarkable tumour specificity of these compounds, and their potency in vitro and in vivo, underscore the potential of HDAC inhibitors as exciting new agents for the treatment of cancer.
Abstract: The opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs) allow gene expression to be exquisitely regulated through chromatin remodelling. Aberrant transcription due to altered expression or mutation of genes that encode HATs, HDACs or their binding partners, is a key event in the onset and progression of cancer. HDAC inhibitors can reactivate gene expression and inhibit the growth and survival of tumour cells. The remarkable tumour specificity of these compounds, and their potency in vitro and in vivo, underscore the potential of HDAC inhibitors as exciting new agents for the treatment of cancer.

1,480 citations

Journal ArticleDOI
TL;DR: The ATM gene is responsible for the rare disorder ataxia-telangiectasia, mutated, and patients show various abnormalities, mainly in their responses to DNA damage, but also in other cellular processes.
Abstract: As its name suggests, the ATM ? 'ataxia-telangiectasia, mutated' ? gene is responsible for the rare disorder ataxia-telangiectasia. Patients show various abnormalities, mainly in their responses to DNA damage, but also in other cellular processes. Although it is hard to understand how a single gene product is involved in so many physiological processes, a clear picture is starting to emerge. online summary

775 citations

Journal ArticleDOI
TL;DR: A key event in the regulation of eukaryotic gene expression is the posttranslational modification of nucleosomal histones, which converts regions of chromosomes into transcriptionally active or inactive chromatin.
Abstract: A key event in the regulation of eukaryotic gene expression is the posttranslational modification of nucleosomal histones, which converts regions of chromosomes into transcriptionally active or inactive chromatin. The most well studied posttranslational modification of histones is the acetylation of epsilon-amino groups on conserved lysine residues in the histones' amino-terminal tail domains. Significant advances have been made in the past few years toward the identification of histone acetyltransferases and histone deacetylases. Currently, there are over a dozen cloned histone acetyltransferases and at least eight cloned human histone deacetylases. Interestingly, many histone deacetylases can function as transcriptional corepressors and, often, they are present in multi-subunit complexes. More intriguing, at least some histone deacetylases are associated with chromatin-remodeling machines. In addition, several studies have pointed to the possible involvement of histone deacetylases in human cancer. The availability of the cloned histone deacetylase genes has provided swift progress in the understanding of the mechanisms of deacetylases, their role in transcription, and their possible role in health and disease.

660 citations

Journal ArticleDOI
Yosef Shiloh1
TL;DR: The protein kinases ATM and ATR are master controllers of some of these networks, acting either in concert or separately to orchestrate the responses to specific types of DNA damage or stalled replication.

604 citations