Sitafloxacin reduces tumor necrosis factor alpha (TNFα) converting enzyme (TACE) phosphorylation and activity to inhibit TNFα release from lipopolysaccharide-stimulated THP-1 cells

Sepsis is a systemic reaction to an infection and resulting in excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study aimed to identify quinolone antibiotics that can reduce tumor necrosis factor alpha (TNFα) production and to elucidate...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2021-12, Vol.11 (1), p.24154-24154, Article 24154
Main Authors: Sakamaki, Ippei, Fukushi, Michika, Ohashi, Wakana, Tanaka, Yukie, Itoh, Kazuhiro, Tomihara, Kei, Yamamoto, Yoshihiro, Iwasaki, Hiromichi
Format: Article
Language:English
Subjects:
631/250
631/326
ADAM17 Protein - metabolism
Antibiotics
Chemokines
Enzymes
Extracellular signal-regulated kinase
Fluoroquinolones - pharmacology
Humanities and Social Sciences
Humans
Inflammation
Lipopolysaccharides
Lipopolysaccharides - toxicity
multidisciplinary
Necrosis
Phosphorylation
Phosphorylation - drug effects
Science
Science (multidisciplinary)
Sepsis
Septic shock
THP-1 Cells
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Sepsis is a systemic reaction to an infection and resulting in excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study aimed to identify quinolone antibiotics that can reduce tumor necrosis factor alpha (TNFα) production and to elucidate mechanisms underlying inhibition of TNFα production. We identified quinolone antibiotics reduced TNFα production in lipopolysaccharide (LPS)-stimulated THP-1 cells. Sitafloxacin (STFX) is a broad-spectrum antibiotic of the quinolone class. STFX effectively suppressed TNFα production in LPS-stimulated THP-1 cells in a dose-dependent manner and increased extracellular signal-regulated kinase (ERK) phosphorylation. The percentage of intracellular TNFα increased in LPS-stimulated cells with STFX compared with that in LPS-stimulated cells. TNFα converting enzyme (TACE) released TNFα from the cells, and STFX suppressed TACE phosphorylation and activity. To conclude, one of the mechanisms underlying inhibition of TNFα production in LPS-stimulated THP-1 cells treated with STFX is the inhibition of TNFα release from cells via the suppression of TACE phosphorylation and activity. STFX may kill bacteria and suppress inflammation. Therefore, it can be effective for sepsis treatment.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-03511-5