Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by enhanced chronic inflammation in the airways, lung parenchyma, and circulation. We investigated whether SUV39H1, a histone methyltransferase, is causatively implicated in the abnormal inflammation observed in COPD. The SUV39H1 and H3K9me3 levels were reduced in peripheral blood mononuclear cells (PBMCs), primary human small airway epithelial cells (HSAEpCs) and lung tissues from COPD patients, which were correlated with poor lung function and the serum IL-8 and IL-6 levels. A specific SUV39H1 inhibitor, chaetocin, induced a distinct COPD panel of inflammatory cytokines in normal PBMCs. Mechanistically, chaetocin reduced the SUV39H1 and H3K9me3 levels in the native IL-8 promoter in normal HSAEpCs, which mimicked unstimulated COPD HSAEpCs and led to decreased HP-1α levels and increased RNA polymerase II levels. SUV39H1 knockdown reproduced the pattern of COPD inflammation, whereas SUV39H1 overexpression in COPD HSAEpCs rescued the H3K9me3 levels and suppressed inflammation. In COPD mice, chaetocin further repressed the SUV39H1/H3K9me3 levels and enhanced inflammation. SUV39H1 epigenetically controls a distinct panel of pro-inflammatory cytokines. Its reduction in COPD leads to a loss of the repressive chromatin mark H3K9me3 and confers an abnormal inflammatory response to stimulators. SUV39H1 and its regulatory pathways are potential therapeutic targets for COPD.

Original languageEnglish
Article number46667
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Jan 1 2017

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Chronic Obstructive Pulmonary Disease
Inflammation
Epithelial Cells
Interleukin-8
Lung
Blood Cells
Cytokines
RNA Polymerase II
Chromatin
Interleukin-6
Pneumonia
Serum

ASJC Scopus subject areas

  • General

Cite this

SUV39H1 reduction is implicated in abnormal inflammation in COPD. / Chen, Tzu Tao; Wu, Sheng Ming; Ho, Shu Chuan; Chuang, Hsiao Chi; Liu, Chien Ying; Chan, Yao Fei; Kuo, Lu Wei; Feng, Po Hao; Liu, Wen Te; Chen, Kuan Yuan; Hsiao, Ta Chih; Juang, Jer Nan; Lee, Kang Yun.

In: Scientific Reports, Vol. 7, 46667, 01.01.2017.

Research output: Contribution to journalArticle

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abstract = "Chronic obstructive pulmonary disease (COPD) is characterized by enhanced chronic inflammation in the airways, lung parenchyma, and circulation. We investigated whether SUV39H1, a histone methyltransferase, is causatively implicated in the abnormal inflammation observed in COPD. The SUV39H1 and H3K9me3 levels were reduced in peripheral blood mononuclear cells (PBMCs), primary human small airway epithelial cells (HSAEpCs) and lung tissues from COPD patients, which were correlated with poor lung function and the serum IL-8 and IL-6 levels. A specific SUV39H1 inhibitor, chaetocin, induced a distinct COPD panel of inflammatory cytokines in normal PBMCs. Mechanistically, chaetocin reduced the SUV39H1 and H3K9me3 levels in the native IL-8 promoter in normal HSAEpCs, which mimicked unstimulated COPD HSAEpCs and led to decreased HP-1α levels and increased RNA polymerase II levels. SUV39H1 knockdown reproduced the pattern of COPD inflammation, whereas SUV39H1 overexpression in COPD HSAEpCs rescued the H3K9me3 levels and suppressed inflammation. In COPD mice, chaetocin further repressed the SUV39H1/H3K9me3 levels and enhanced inflammation. SUV39H1 epigenetically controls a distinct panel of pro-inflammatory cytokines. Its reduction in COPD leads to a loss of the repressive chromatin mark H3K9me3 and confers an abnormal inflammatory response to stimulators. SUV39H1 and its regulatory pathways are potential therapeutic targets for COPD.",
author = "Chen, {Tzu Tao} and Wu, {Sheng Ming} and Ho, {Shu Chuan} and Chuang, {Hsiao Chi} and Liu, {Chien Ying} and Chan, {Yao Fei} and Kuo, {Lu Wei} and Feng, {Po Hao} and Liu, {Wen Te} and Chen, {Kuan Yuan} and Hsiao, {Ta Chih} and Juang, {Jer Nan} and Lee, {Kang Yun}",
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AU - Chen, Tzu Tao

AU - Wu, Sheng Ming

AU - Ho, Shu Chuan

AU - Chuang, Hsiao Chi

AU - Liu, Chien Ying

AU - Chan, Yao Fei

AU - Kuo, Lu Wei

AU - Feng, Po Hao

AU - Liu, Wen Te

AU - Chen, Kuan Yuan

AU - Hsiao, Ta Chih

AU - Juang, Jer Nan

AU - Lee, Kang Yun

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N2 - Chronic obstructive pulmonary disease (COPD) is characterized by enhanced chronic inflammation in the airways, lung parenchyma, and circulation. We investigated whether SUV39H1, a histone methyltransferase, is causatively implicated in the abnormal inflammation observed in COPD. The SUV39H1 and H3K9me3 levels were reduced in peripheral blood mononuclear cells (PBMCs), primary human small airway epithelial cells (HSAEpCs) and lung tissues from COPD patients, which were correlated with poor lung function and the serum IL-8 and IL-6 levels. A specific SUV39H1 inhibitor, chaetocin, induced a distinct COPD panel of inflammatory cytokines in normal PBMCs. Mechanistically, chaetocin reduced the SUV39H1 and H3K9me3 levels in the native IL-8 promoter in normal HSAEpCs, which mimicked unstimulated COPD HSAEpCs and led to decreased HP-1α levels and increased RNA polymerase II levels. SUV39H1 knockdown reproduced the pattern of COPD inflammation, whereas SUV39H1 overexpression in COPD HSAEpCs rescued the H3K9me3 levels and suppressed inflammation. In COPD mice, chaetocin further repressed the SUV39H1/H3K9me3 levels and enhanced inflammation. SUV39H1 epigenetically controls a distinct panel of pro-inflammatory cytokines. Its reduction in COPD leads to a loss of the repressive chromatin mark H3K9me3 and confers an abnormal inflammatory response to stimulators. SUV39H1 and its regulatory pathways are potential therapeutic targets for COPD.

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