Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression
Abstract Background Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, and is primarily characterized by an uncontrolled systemic inflammatory response. In the present study, we developed an effective adjunct therapy mediated by a novel mechanism, to at...
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | Journal of Inflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12950-018-0179-6 |
| _version_ | 1818501856099303424 |
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| author | Wen-Feng Fang Yu-Mu Chen Chiung-Yu Lin Hui-Lin Huang Hua Yeh Ya-Ting Chang Kuo-Tung Huang Meng-Chih Lin |
| author_facet | Wen-Feng Fang Yu-Mu Chen Chiung-Yu Lin Hui-Lin Huang Hua Yeh Ya-Ting Chang Kuo-Tung Huang Meng-Chih Lin |
| author_sort | Wen-Feng Fang |
| collection | DOAJ |
| description | Abstract Background Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, and is primarily characterized by an uncontrolled systemic inflammatory response. In the present study, we developed an effective adjunct therapy mediated by a novel mechanism, to attenuate overt inflammation. LPS-treated macrophages were adopted as an in vitro model of endotoxin-induced inflammation during sepsis. Experiments were carried out using primary mouse peritoneal macrophages and the murine macrophage cell line RAW264.7, to elucidate the mechanisms by which HDAC2 modulates endotoxin-induced inflammation. Results Results revealed that PAI-1, TNF, and MIP-2 expression were inhibited by theophylline, an HDAC2 enhancer, in a RAW macrophage cell line, following LPS-induced inflammation. Thus, HDAC2 plays an important role in immune defense by regulating the expression of inflammatory genes via the c-Jun/PAI-1 pathway. During LPS-induced inflammation, overexpression of HDAC2 was found to inhibit PAI-1, TNF, and MIP-2 expression. Following LPS stimulation, HDAC2 knockdown increased nuclear translocation and DNA binding of c-Jun to the PAI-1 gene promoter, thereby activating PAI-1 gene transcription. Furthermore, inhibition of PAI-1 by TM5275 alone or in combination with theophylline notably suppressed TNF and MIP-2 expression. Conclusion HDAC2 can attenuate lipopolysaccharide-induced inflammation by regulating c-Jun and PAI-1 expression in macrophages. |
| first_indexed | 2024-12-10T21:02:03Z |
| format | Article |
| id | doaj.art-c9b906cba447417b969c8ba79d43ead7 |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-12-10T21:02:03Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-c9b906cba447417b969c8ba79d43ead72022-12-22T01:33:46ZengBMCJournal of Inflammation1476-92552018-01-0115111110.1186/s12950-018-0179-6Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expressionWen-Feng Fang0Yu-Mu Chen1Chiung-Yu Lin2Hui-Lin Huang3Hua Yeh4Ya-Ting Chang5Kuo-Tung Huang6Meng-Chih Lin7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineAbstract Background Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, and is primarily characterized by an uncontrolled systemic inflammatory response. In the present study, we developed an effective adjunct therapy mediated by a novel mechanism, to attenuate overt inflammation. LPS-treated macrophages were adopted as an in vitro model of endotoxin-induced inflammation during sepsis. Experiments were carried out using primary mouse peritoneal macrophages and the murine macrophage cell line RAW264.7, to elucidate the mechanisms by which HDAC2 modulates endotoxin-induced inflammation. Results Results revealed that PAI-1, TNF, and MIP-2 expression were inhibited by theophylline, an HDAC2 enhancer, in a RAW macrophage cell line, following LPS-induced inflammation. Thus, HDAC2 plays an important role in immune defense by regulating the expression of inflammatory genes via the c-Jun/PAI-1 pathway. During LPS-induced inflammation, overexpression of HDAC2 was found to inhibit PAI-1, TNF, and MIP-2 expression. Following LPS stimulation, HDAC2 knockdown increased nuclear translocation and DNA binding of c-Jun to the PAI-1 gene promoter, thereby activating PAI-1 gene transcription. Furthermore, inhibition of PAI-1 by TM5275 alone or in combination with theophylline notably suppressed TNF and MIP-2 expression. Conclusion HDAC2 can attenuate lipopolysaccharide-induced inflammation by regulating c-Jun and PAI-1 expression in macrophages.http://link.springer.com/article/10.1186/s12950-018-0179-6Histone deacetylase 2 (HDAC2)Plasminogen activator inhibitor (PAI)Lipopolysaccharide (LPS) |
| spellingShingle | Wen-Feng Fang Yu-Mu Chen Chiung-Yu Lin Hui-Lin Huang Hua Yeh Ya-Ting Chang Kuo-Tung Huang Meng-Chih Lin Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression Journal of Inflammation Histone deacetylase 2 (HDAC2) Plasminogen activator inhibitor (PAI) Lipopolysaccharide (LPS) |
| title | Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression |
| title_full | Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression |
| title_fullStr | Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression |
| title_full_unstemmed | Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression |
| title_short | Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression |
| title_sort | histone deacetylase 2 hdac2 attenuates lipopolysaccharide lps induced inflammation by regulating pai 1 expression |
| topic | Histone deacetylase 2 (HDAC2) Plasminogen activator inhibitor (PAI) Lipopolysaccharide (LPS) |
| url | http://link.springer.com/article/10.1186/s12950-018-0179-6 |
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