Obeticholic acid attenuates human immunodeficiency virus/alcohol metabolism-induced pro-fibrotic activation in liver cells

Figure 1 Obeticholic acid attenuates apoptosis in acetaldehyde-generating system-human immunodeficiency virus-exposed Huh7. 5-CYP cells. A: Cleaved caspase 3 (western blot, representative blot); B: Cleaved caspase 3 cleavage, quantification; C: Cleaved PARP (western blot, representative blot); D: Cleaved PARP, quantification; E: M30 ELISA. All data were obtained from 3 independent experiments and presented as mean ± SEM. Bars with different letters are significantly different at P ≤ 0.05. AGS: Acetaldehyde-generating system; HIV: Human immunodeficiency virus; OCA: Obeticholic acid.

Figure 2 Effects of obeticholic acid on p53 mRNA and reactive oxygen species production in human immunodeficiency virus-infected Huh7. 5-CYP cells exposed to acetaldehyde-generating system. A: p53 mRNA; B: Reactive oxygen species production. All data were obtained from 3 independent experiments and presented as mean ± SEM. Bars with different letters are significantly different at P ≤ 0.05. AGS: Acetaldehyde-generating system; HIV: Human immunodeficiency virus; OCA: Obeticholic acid.

Figure 3 Obeticholic acid suppresses human immunodeficiency virus expression in Huh7. 5-CYP cells exposed to acetaldehyde-generating system + human immunodeficiency virus. A: Human immunodeficiency virus (HIV) gagRNA; B: p24; C: HIV DNA. All data were obtained from 3 independent experiments and presented as mean ± SEM. Bars with different letters are significantly different at P ≤ 0.05. AGS: Acetaldehyde-generating system; HIV: Human immunodeficiency virus; OCA: Obeticholic acid.

Figure 4 Restorative effects of obeticholic acid on proteasomal and lysosomal activities in acetaldehyde-generating system-human immunodeficiency virus-exposed Huh7. 5-CYP cells. A: Chymotrypsin-like activity, proteasome; B: Trypsin-like activity, proteasome; C: Cathepsin B activity, lysosome; D: Cathepsin L activity, lysosome. All data were obtained from 3 independent experiments and presented as mean ± SEM. Bars with different letters are significantly different at P ≤ 0.05. AGS: Acetaldehyde-generating system; HIV: Human immunodeficiency virus; OCA: Obeticholic acid.

Figure 5 Anti-fibrotic effects of obeticholic acid on hepatic stellate cells activated by engulfment of apoptotic Huh7. 5-CYP cells. A: Col1A1 mRNA; B: Transforming growth factor-β mRNA. All data were obtained from 3 independent experiments and presented as mean ± SEM. Bars with different letters are significantly different at P ≤ 0.05. TGF: Transforming growth factor; HIV: Human immunodeficiency virus; OCA: Obeticholic acid.

Figure 6 Obeticholic acid suppresses acetaldehyde-generating system-human immunodeficiency virus-induced activation of inflammasome, mRNAs. A: NLRP3; B: Caspase 1; C: Interleukin (IL)-6; D: IL-1β. All data were obtained from 3 independent experiments and presented as mean ± SEM. Bars with different letters are significantly different at P ≤ 0.05. IL-6 and IL-1β: -interleukins B and IL-1β; HIV: Human immunodeficiency virus; OCA: Obeticholic acid.