期刊
INFLAMMATION RESEARCH
卷 67, 期 4, 页码 315-326出版社
SPRINGER BASEL AG
DOI: 10.1007/s00011-017-1123-6
关键词
N6-isopentenyladenosine; Inflammation; NF kappa B; STAT3; Cystic fibrosis; Selenoproteins
资金
- Associazione Italiana Ricerca sul Cancro (AIRC) [IG 13312, IG 18999]
- University of Salerno [1211/2017, ORSA177721]
- Fondazione Umberto Veronesi (FUV) [1072]
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. TNF alpha-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 kappa B activity, luciferase assay was performed on TNF alpha-stimulated HEK293/T cells transfected with a NF kappa B reporter plasmid. We demonstrated for the first time that iPA prevents IL-8 and RANTES release in TNF alpha-stimulated CF cells and this effect is mediated by increasing the expression of the direct NF kappa B inhibitor I kappa B alpha and decreasing the levels of STAT3. Consistent with this, we showed that iPA inhibited TNF alpha-mediated NF kappa 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. Our findings indicate that iPA can exert anti-inflammatory activity especially in the cases of excessive inflammatory response as in CF.
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