Hirsutanol A attenuates lipopolysaccharide-mediated matrix metalloproteinase 9 expression and cytokines production and improves endotoxemia-induced acute sickness behavior and acute lung injury

Jing Shiun Jan, Chih Hao Yang, Mong-Heng Wang, Fan Li Lin, Jing Lun Yen, Irene Hsieh, Maksim Khotimchenko, Tzong Huei Lee, George Hsiao

Research output: Contribution to journalArticle

Abstract

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-1β 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.

Original languageEnglish (US)
Article number360
JournalMarine Drugs
Volume17
Issue number6
DOIs
StatePublished - Jun 17 2019

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Illness Behavior
Endotoxemia
Acute Lung Injury
Matrix Metalloproteinase 9
Lipopolysaccharides
Cytokines
Sepsis
Alveolar Epithelial Cells
Rhodophyta
Tissue Inhibitor of Metalloproteinase-1
Lung Injury
Matrix Metalloproteinases
Interleukin-1
hirsutanol A
Monocytes
Interleukin-6
Hippocampus
Edema
Fungi
Anxiety

Keywords

  • Acute lung injury (ALI)
  • Acute sickness behavior
  • Interleukin (IL)
  • Lipopolysaccharide (LPS)
  • Matrix metalloproteinases-9 (MMP-9)
  • Signal transducer and activator of transcription 3 (STAT3)

ASJC Scopus subject areas

  • Drug Discovery

Cite this

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.

In: Marine Drugs, Vol. 17, No. 6, 360, 17.06.2019.

Research output: Contribution to journalArticle

Jan, Jing Shiun ; Yang, Chih Hao ; Wang, Mong-Heng ; Lin, Fan Li ; Yen, Jing Lun ; Hsieh, Irene ; Khotimchenko, Maksim ; Lee, Tzong Huei ; Hsiao, George. / Hirsutanol A attenuates lipopolysaccharide-mediated matrix metalloproteinase 9 expression and cytokines production and improves endotoxemia-induced acute sickness behavior and acute lung injury. In: Marine Drugs. 2019 ; Vol. 17, No. 6.
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abstract = "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-1β 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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T1 - Hirsutanol A attenuates lipopolysaccharide-mediated matrix metalloproteinase 9 expression and cytokines production and improves endotoxemia-induced acute sickness behavior and acute lung injury

AU - Jan, Jing Shiun

AU - Yang, Chih Hao

AU - Wang, Mong-Heng

AU - Lin, Fan Li

AU - Yen, Jing Lun

AU - Hsieh, Irene

AU - Khotimchenko, Maksim

AU - Lee, Tzong Huei

AU - Hsiao, George

PY - 2019/6/17

Y1 - 2019/6/17

N2 - 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-1β 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.

AB - 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-1β 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.

KW - Acute lung injury (ALI)

KW - Acute sickness behavior

KW - Interleukin (IL)

KW - Lipopolysaccharide (LPS)

KW - Matrix metalloproteinases-9 (MMP-9)

KW - Signal transducer and activator of transcription 3 (STAT3)

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U2 - 10.3390/md17060360

DO - 10.3390/md17060360

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VL - 17

JO - Marine Drugs

JF - Marine Drugs

SN - 1660-3397

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