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Hirsutanol A Attenuates Lipopolysaccharide-Mediated Matrix Metalloproteinase 9 Expression and Cytokines Production and Improves Endotoxemia-Induced Acute Sickness Behavior and Acute Lung Injury.
Jan, Jing-Shiun; Yang, Chih-Hao; Wang, Mong-Heng; Lin, Fan-Li; Yen, Jing-Lun; Hsieh, Irene; Khotimchenko, Maksim; Lee, Tzong-Huei; Hsiao, George.
Afiliação
  • Jan JS; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. d119101004@tmu.edu.tw.
  • Yang CH; Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. d119101004@tmu.edu.tw.
  • Wang MH; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. chyang@tmu.edu.tw.
  • Lin FL; Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. chyang@tmu.edu.tw.
  • Yen JL; Department of Physiology, Augusta University, Augusta, GA 30912, USA. mwang@augusta.edu.
  • Hsieh I; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. fllin@tmu.edu.tw.
  • Khotimchenko M; Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. fllin@tmu.edu.tw.
  • Lee TH; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. m120102039@tmu.edu.tw.
  • Hsiao G; Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. m120102039@tmu.edu.tw.
Mar Drugs ; 17(6)2019 Jun 17.
Article em En | MEDLINE | ID: mdl-31213027
Activated human monocytes/macrophages, which increase the levels of matrix metalloproteinases (MMPs) and pro-inflammatory cytokines, are the essential mechanisms for the progression of sepsis. In the present study, we determined the functions and mechanisms of hirsutanolA (HA), which is isolated from the red alga-derived marine fungus Chondrostereum sp. NTOU4196, on the production of pro-inflammatory mediators produced from lipopolysaccharide (LPS)-treated THP-1 cells. Our results showed that HA suppressed LPS-triggered MMP-9-mediated gelatinolysis and expression of protein and mRNA in a concentration-dependent manner without effects on TIMP-1 activity. Also, HA significantly attenuated the levels of TNF-α, IL-6, and IL-1ß from LPS-treated THP-1 cells. Moreover, HA significantly inhibited LPS-mediated STAT3 (Tyr705) phosphorylation, IκBα degradation and ERK1/2 activation in THP-1 cells. In an LPS-induced endotoxemia mouse model, studies indicated that HA pretreatment improved endotoxemia-induced acute sickness behavior, including acute motor deficits and anxiety-like behavior. HA also attenuated LPS-induced phospho-STAT3 and pro-MMP-9 activity in the hippocampus. Notably, HA reduced pathologic lung injury features, including interstitial tissue edema, infiltration of inflammatory cells and alveolar collapse. Likewise, HA suppressed the induction of phospho-STAT3 and pro-MMP-9 in lung tissues. In conclusion, our results provide pharmacological evidence that HA could be a useful agent for treating inflammatory diseases, including sepsis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sesquiterpenos / Citocinas / Metaloproteinase 9 da Matriz / Lesão Pulmonar Aguda / Comportamento de Doença Tipo de estudo: Etiology_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sesquiterpenos / Citocinas / Metaloproteinase 9 da Matriz / Lesão Pulmonar Aguda / Comportamento de Doença Tipo de estudo: Etiology_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article