Resveratrol

Histone acetyltransferase inhibitor Garcinol (GAR), SIRT1 activator Resveratrol (RES), SIRT1 inhibitor Nicotinamide (NIC) and NF-κB inhibitor BAY 11-7082 (BAY) were obtained from Santa Cruz (Santa Cruz, CA). Antibodies against HMGB1 and β-actin were purchased from Cell Signaling Technology (Danvers, MA). Anti-acetyl lysine antibody (clone Kac-01) was purchased from PTM Biolab (Hangzhou, China). siRNAs were purchased from biotend (Shanghai, China). The bovine serum albumin (BSA) was purchased from Dingguo (Nanjing, China).

The Staphylococcus aureus JE2 wild type (WT) strain and derivative mutants used in this study are highlighted in Table 1. Antimicrobial peptides used in this study included histatin-5 (Innovagen, Sweden), LL-37 (Isca Biochemicals, United Kingdom) and hBD1-4 (Innovagen, Sweden), as well as polymyxin B Etests (bioMérieux, France). We used the ATP synthase inhibitor resveratrol (Santa Cruz Biotechnology). Bacterial strains were routinely cultured at 37 °C in tryptic soy broth (TSB) or on tryptic soy agar (TSA).Table 1

Strains and mutants used.

Organism	Description and genotype	Source
S. aureus	JE2, CA-MRSA USA300
S. aureus	JE2 menD::ΦNΣ	60 (link)
S. aureus	JE2 atpA::ΦNΣ	60 (link)
S. aureus	JE2 atpB::ΦNΣ	60 (link)
S. aureus	JE2 atpG::ΦNΣ	60 (link)
S. aureus	atpA+—Strain with allelic exchange of the transposon insertion (atpA::ΦNΣ) with the intact atpA gene	25 (link)

Flavourzyme^® 1000 L (EC 3.4.11.1, 500 leucine amino peptidase units (LAPU)/g from Aspergillus oryzae) was kindly provided by Novozymes (Bagsværd, Denmark). ACE (EC 3.4.15.1), 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), picrylsulfonic acid and acetonitrile for HPLC were purchased from Sigma-Aldrich (Madrid, Spain). Captopril (PubChem CID: 44093) and resveratrol were provided by Santa Cruz Biotechnology (Dallas, TX, USA) and Carl Roth (Karlsruhe, Germany), respectively. Folin–Ciocalteu reagent, coumaric acid, quercetin, gallic acid, catechin, and epicatechin were purchased from Fluka/Sigma-Aldrich. 4-Hydroxybenzoic acid, caffeic acid, procyanidin dimer B2, vanillic acid, and malvidin-3-O-glucoside were purchased from Extrasynthése (Lyon, France). Ferulic acid, cyanidin-3-O-rutinoside, and peonidin-3-O-rutinoside were purchased from PhytoLab (Vestenbergsgreuth, Germany). Analytical grade reagents were always used.

Commercially available Hep3B, RAW264.7 cells (ECACC, Sigma-Aldrich, St. Louis, MO, USA) were used. LX2 cells were kindly given by Dr. Ramón Bataller (IDIBAPS, Barcelona, Spain). All cell lines are mycoplasma-free. Human recombinant TNF (Peprotech, Rocky Hill, NJ, USA), LPS (E. coli 0111:B4, Sigma-Aldrich) were administered to cells at 50 ng/ml. CTSB inhibitor (CA-074 methyl ester, Sigma-Aldrich) was given at 25 μM to primary hepatocytes, HSCs, Hep3B and LX2 cells and at 75 μM to KCs and RAW264.7 cells. CTSS inhibitor (Z-FL-COCHO, Calbiochem, San Diego, CA, USA) was given at 10 μM to primary hepatocytes, HSCs, Hep3B and LX2 cells and at 7.5 μM to KCs. Resveratrol (100 μM) and Tenovin-6 (10 μM) (Santa Cruz Biotechnology, Dallas, TX, USA) were given to LX2 cells. Control and human SIRT1 shRNA lentiviral particles commercially available were used (Santa Cruz Biotechnology).

[Triphenylphosphine-1,3-diethylbenzylimidazol-2-ylidene)]gold(I) iodide (MC4) was synthesized as described^{19 (link),20 (link),52 (link)}. TCDD was purchased from Sigma Aldrich (Germany). Resveratrol and Auranofin were from Santa Cruz (Germany). Antibodies of AHR (Biomol, Germany, AP5533C, 1:1000) and CYP1A1 were obtained from Abgent (Biomol, Germany, F50940, 1:1000). ACTIN (SC-47778, 1:1000) and VINCULIN (SC-73614) were from Santa Cruz. SMAD4 (9515, 1:1000), pSMAD3 (9520), and SMAD3 (9523, 1:1000) were from Cell Signaling (NEB, Germany).