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Lipid-deprived monocytes activate the mevalonate pathway and increase the early responsiveness to type I IFN in a prenylation-dependent manner. A Monocytes from healthy controls were cultured 18 hrs with NS or LPDS. The expression of HMGCR , FDPS , GGPS , FDFT1 and PGGT1b genes was analyzed by real-time RT-PCR. Data are from 5 donors. Bars represent means and SD. * P < 0.05, *** P < 0.001, by paired T test. B-C Monocytes were cultured 18 hrs with NS, LPDS, or LPDS supplemented with geranyl-geranyl transferase inhibitor (GGTi 30 μM), then IFNAR expression was analyzed by flow cytometry. ( B ) Histogram overlay of IFNAR gMFI, and cumulative analysis of the relative gMFI (calculated by subtracting the respective fmo control for each sample), are shown. Data are from 7 donors from 2 independent experiments. ( C ) IFN (40.000 IU/mL) was added in the last 15 minutes of culture, then STAT1 phosphorylation was analyzed by flow cytometry. Histograms and cumulative analysis of gMFI of pSTAT1 are shown. Data are from 6 donors from 2 independent experiments. Bars represent means and SD. * P < 0.05, by 1way ANOVA with Dunnett’s multiple comparisons test

Journal: Journal of Translational Medicine

Article Title: Lipid deprivation amplifies type I IFN responses in monocytes through prenylation: insights from familial combined hypolipidemia type 2

doi: 10.1186/s12967-025-07448-5

Figure Lengend Snippet: Lipid-deprived monocytes activate the mevalonate pathway and increase the early responsiveness to type I IFN in a prenylation-dependent manner. A Monocytes from healthy controls were cultured 18 hrs with NS or LPDS. The expression of HMGCR , FDPS , GGPS , FDFT1 and PGGT1b genes was analyzed by real-time RT-PCR. Data are from 5 donors. Bars represent means and SD. * P < 0.05, *** P < 0.001, by paired T test. B-C Monocytes were cultured 18 hrs with NS, LPDS, or LPDS supplemented with geranyl-geranyl transferase inhibitor (GGTi 30 μM), then IFNAR expression was analyzed by flow cytometry. ( B ) Histogram overlay of IFNAR gMFI, and cumulative analysis of the relative gMFI (calculated by subtracting the respective fmo control for each sample), are shown. Data are from 7 donors from 2 independent experiments. ( C ) IFN (40.000 IU/mL) was added in the last 15 minutes of culture, then STAT1 phosphorylation was analyzed by flow cytometry. Histograms and cumulative analysis of gMFI of pSTAT1 are shown. Data are from 6 donors from 2 independent experiments. Bars represent means and SD. * P < 0.05, by 1way ANOVA with Dunnett’s multiple comparisons test

Article Snippet: RT-PCR was performed to analyze the expression of selected genes using the following Taqman assays: HMGCR Hs00168352_m1, FDFT1 Hs00926054_m1, PGGT1B Hs00270701_m1, GGPS1 Hs01546492_g1, FDPS Hs01578769_g1, MX1 Hs00895608_m1, IFIT1 Hs03027069_s1, ISG15 Hs01921425_s1.

Techniques: Cell Culture, Expressing, Quantitative RT-PCR, Flow Cytometry, Control, Phospho-proteomics