Fig. 4: 4-OI and DMF limit SARS-CoV2 and HSV induced inflammatory responses. | Nature Communications

Fig. 4: 4-OI and DMF limit SARS-CoV2 and HSV induced inflammatory responses.

From: SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

Fig. 4

a–c Calu-3 treated with 4-OI (125 µM, 48 h) before SARS-CoV2 infection (MOI 0.5, 48 h) and qPCR analysis. a, b, and c are pooled data from three independent experiments in triplicates. d–f HAE-cultures treated with 4-OI before SARS-CoV2 infection for 24 h and analysis by qPCR. Data are from two donors. g–i Calu-3 cells with DMF (48 h) before SARS-CoV2 infection. Analysis by qPCR. In (g, h, and i), display pooled data from three independent experiments in duplicates and triplicates. (d–f), data are representative of four independent HAE-cultures. (j) Healthy PBMCs treated with 4-OI before infection and qPCR analysis. Data are representative of two donors. (k) PBMCs from four COVID-19 patients (k) and 2 healthy controls (HC) treated with 4-OI before qPCR. (l-m) HaCaTs treated with 4-OI before stimulation with M8 for 6 h followed by qPCR. Data represent one experiment in triplicate. n HaCaT cells with siRNAs before M8 treatment for 3 h followed by immunoblotting. Data are representative of two independent experiments. o HaCaTs treated with siRNA for 72 h before 4-OI and stimulation with M8. Analysis by immunoblotting. Data representative of two independent experiments. o-q HEK293 and HaCaTs transfected with expression-plasmids before 4-OI. In (q), HaCaTs were treated with siRNAs for 72 h before plasmid transfection. Analysis by qPCR and immunoblotting. Data in (p) are from one experiment performed in triplicate. Data displayed in (q) is representative of two independent experiments. (r–t) HaCaTs treated with 4-OI before infection with HSV1 or transfection with dsDNA. Analysis by qPCR and immunoblotting at 6 and 3 h respectively. (n–t), data are from one experiment representative of two independent experiments. Data in (r) and (s) are representative of two independent experiments in triplicates. Bars indicate mean ± s.e.m. Unless otherwise stated, all statistical analysis by two-tailed Mann–Whitney test where *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. P values:, a: p < 0.0001(IFNB1) and p < 0.0001(CXCL10), b: p < 0.0001(CCL5) and p < 0.0001(TNFA) and p < 0.0001(IL1B), c: p < 0.0001, d: p = 0.0286(IFNB1) and p = 0.0286(CXCL10), e: p = 0.0286(TNFA) and p = 0.0286(CCL5), f: p = 0.0286, g: p = 0.0003(IFNB1) and p = 0.0002(CXCL10), h: p = 0.0002(CCL5) and p = 0.0003(TNFA), i: p = 0.0011, j: p = 0.0005 (two-tailed t test, SARS-CoV2) and p = 0.0053 (two-tailed t test, SeV), p: p = 0.0092 (two-tailed t test). Source data are provided as a Source Data file.

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