Protection against Lipopolysaccharide-Induced Endotoxemia by Terrein Is Mediated by Blocking Interleukin-1β and Interleukin-6 Production

Terrein is a fungal metabolite and has been known to exert anti-melanogenesis, anti-cancer, and anti-bacterial activities. However, its role in endotoxemia has never been investigated until now. In the present study, we examined the effect of terrein on lipopolysaccharide (LPS)-induced endotoxemia i...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-11, Vol.15 (11), p.1429
Main Authors: Yoon, Yeo Dae, Lee, Myeong Youl, Choi, Byeong Jo, Lee, Chang Woo, Lee, Hyunju, Kwon, Joo-Hee, Yang, Jeong-Wook, Kang, Jong Soon
Format: Article
Language:English
Subjects:
Aspergillus
Biological activity
Chemical properties
Cytokines
endotoxemia
Endotoxins
Gene expression
Health aspects
interleukin-1β
interleukin-6
Interleukins
NF-κB
Phosphorylation
Physiological aspects
Sepsis
terrein
Transcription factors
Tumor necrosis factor-TNF
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Summary:Terrein is a fungal metabolite and has been known to exert anti-melanogenesis, anti-cancer, and anti-bacterial activities. However, its role in endotoxemia has never been investigated until now. In the present study, we examined the effect of terrein on lipopolysaccharide (LPS)-induced endotoxemia in mice and characterized the potential mechanisms of action. Treatment with terrein increased the survival of mice and decreased the production of inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an LPS-induced endotoxemia model. In addition, terrein suppressed the LPS-induced production of IL-1β and IL-6 in RAW 264.7 cells, a murine macrophage-like cell line, and the mRNA expression of IL-1β and IL-6 was also inhibited by terrein in LPS-stimulated RAW 264.7 cells. Further study demonstrated that terrein blocked LPS-induced phosphorylation of p65 subunit of nuclear factor (NF)/κB and the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) was also suppressed by terrein treatment. Collectively, these results suggest that terrein exerts a protective effect again LPS-induced endotoxemia in mice by blocking the production of inflammatory cytokines. Our results also suggest that the anti-inflammatory effect of terrein might be mediated, at least in part, by blocking the activation of NF-κB, JNK, and p38 MAPK signaling pathways.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph15111429