TY - JOUR
T1 - Modulatory effects of osthole on lipopolysaccharides-induced inflammation in Caco-2 cell monolayer and co-cultures with THP-1 and THP-1-derived macrophages
AU - Kordulewska, Natalia K.
AU - Topa, Justyna
AU - Tańska, Małgorzata
AU - Cieślińska, Anna
AU - Fiedorowicz, Ewa
AU - Savelkoul, Huub F.J.
AU - Jarmołowska, Beata
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - Gene expression
KW - Interleukin
KW - Permeability
KW - Pro-inflammatory cytokine
KW - Transepithelial electrical resistance
U2 - 10.3390/nu13010123
DO - 10.3390/nu13010123
M3 - Article
AN - SCOPUS:85098854143
SN - 2072-6643
VL - 13
SP - 1
EP - 16
JO - Nutrients
JF - Nutrients
IS - 1
M1 - 123
ER -