|
KMID : 1101420230550040306
|
|
Korean Journal of Clinical Laboratory Science
2023 Volume.55 No. 4 p.306 ~ p.313
|
|
|
Protective Effect of Niclosamide on Lipopolysaccharide-induced Sepsis in Mice by Modulating STAT3 Pathway
|
|
Jang Se-Gwang
|
|
|
Abstract
|
|
|
Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β.
Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.
|
|
|
KEYWORD
|
|
|
Lipopolysaccharides, Niclosamide, Sepsis, STAT3 transcription factor
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|
|