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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Inflamm+Res
2018 ; 67
(4
): 315-326
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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[Apr]; 67
(4
): 315-326
PMID29230506
show 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.