Abstract
Selonsertib (GS-4997), a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in a phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). Inflammation is a defense against an effect that can damage the tissue or organ itself. Cytokines are the agents that play a key role in acute inflammation and one of the most important cytokine proteins, IL-1β. In this study, we investigated whether selonsertib and diclofenac sodium (positive control) could inhibit IL-1β caused by two different LPS (Salmonella enterica serotype enteritidis and Escherichia coli O111:B4) stimulated on THP-1 cell line. As a result of the WST-1 assay, the inhibitory concentration of diclofenac sodium at doses of IC50 of 32.5 μM/mL and selonsertib was calculated to be 120 μM/mL. The immunological responses of diclofenac sodium and selonsertib (IL-1β) in different LPS-stimulated THP-1 cells were assessed cytometrically: diclofenac sodium and Selonsertib were found to be effective in stimulation from E. coli. The results showed that selonsertib had a significantly anti-inflammatory effect like diclofenac sodium.
Keywords:
Antiinflammation; ASK1; IL-1β; Selonsertib (GS-4997).
HIGHLIGHTS
• Selonsertib is an ASK-1 inhibitor.
• Selonsertib had a significantly anti-inflammatory effect like diclofenac sodium.
• Selonsertib has been shown to have a pro-inflammatory effect rather than an anti-inflammatory effect.
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