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Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Inflamm+Res 2018 ; 67 (4): 315-26 Nephropedia Template TP
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The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NF?B and STAT3 pathways in cystic fibrosis cells #MMPMID29230506
Santoro A; Ciaglia E; Nicolin V; Pescatore A; Prota L; Capunzo M; Ursini MV; Nori SL; Bifulco M
Inflamm Res 2018[]; 67 (4): 315-26 PMID29230506show ga
Objective: N6-isopentenyladenosine (iPA) is an intermediate of the mevalonate pathway that exhibits various anti-cancer effects. However, studies on its anti-inflammatory activity are scarce and underlying molecular mechanisms are unknown. Therefore, we aimed to investigate the ability of iPA to exert anti-inflammatory effects in the human cystic fibrosis (CF) cell model of exacerbated inflammation. Materials and methods: TNF?-stimulated CF cells CuFi-1 and its normal counterpart NuLi-1 were pre-treated with increasing concentrations of iPA and cell viability and proliferation were assessed by MTT and BrdU assays. The effect of iPA on IL-8 and RANTES secretion was determined by ELISA, and the activation and expression of signaling molecules and selenoproteins were studied by Western blot. To assess the direct effect of iPA on NF?B activity, luciferase assay was performed on TNF?-stimulated HEK293/T cells transfected with a NF?B reporter plasmid. Results: We demonstrated for the first time that iPA prevents IL-8 and RANTES release in TNF?-stimulated CF cells and this effect is mediated by increasing the expression of the direct NF?B inhibitor I?B? and decreasing the levels of STAT3. Consistent with this, we showed that iPA inhibited TNF?-mediated NF?B activation in HEK/293T cells. Finally, we also found that iPA improved the levels of glutathione peroxidase 1 and thioredoxin reductase 1 only in CF cells suggesting its ability to maintain sufficient expression of these anti-oxidant selenoproteins. Conclusions: Our findings indicate that iPA can exert anti-inflammatory activity especially in the cases of excessive inflammatory response as in CF.