Modulatory effects of osthole on lipopolysaccharides-induced inflammation in Caco-2 cell monolayer and co-cultures with THP-1 and THP-1-derived macrophages

Natalia K. Kordulewska*, Justyna Topa, Małgorzata Tańska, Anna Cieślińska, Ewa Fiedorowicz, Huub F.J. Savelkoul, Beata Jarmołowska

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β,-6,-8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/µL for IL1R1 and COX-2 (p < 0.01) and 300 ng/µL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

Original languageEnglish
Article number123
Pages (from-to)1-16
Number of pages16
JournalNutrients
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Gene expression
  • Interleukin
  • Permeability
  • Pro-inflammatory cytokine
  • Transepithelial electrical resistance

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