The activation of SIRT1 ameliorates BPDE‐induced inflammatory damage in BEAS‐2B cells via HMGB1/TLR4/NF‐κB pathway

Abstract

Benzo(a)pyrene‐7,8‐dihydrodiol‐9,10‐epoxide (BPDE), the metabolite of environmental pollutant benzo(a)pyrene (B(a)P) could induce pulmonary toxicity and inflammation. SIRT1, an NAD+ ‐dependent histone deacetylase, is known to regulate inflammation in the occurrence and development of various diseases, but its effects on BPDE‐induced acute lung injury are still unknown. The present study aimed to explore the role of SIRT1 in BPDE‐induced acute lung injury. Here, human bronchial epithelial (HBE) cells (BEAS‐2B) cells were stimulated with BPDE at different concentrations (0.50, 0.75, and 1.00 μmol/L) for 24 h, we found that the levels of cytokines in the supernatant were increased and the expression of SIRT1 in cells was down‐regulated, at the same time, BPDE stimulation up‐regulated the protein expression of HMGB1, TLR4, and p‐NF‐κBp65 in BEAS‐2B cells. Then the activator and inhibitor of SIRT1 were used before BPDE exposure, it was shown that the activation of SIRT1 significantly attenuated the levels of inflammatory cytokines and HMGB1, and reduced the expression of HMGB1, AC‐HMGB1, TLR4, and p‐NF‐κBp65 protein; while these results were reversed by the inhibition of SIRT1. This study revealed that the SIRT1 activation may protect against BPDE‐induced inflammatory damage in BEAS‐2B cells by regulating the HMGB1/TLR4/NF‐κB pathway.

Azadirachtin Attenuates Carcinogen Benzo(a) Pyrene-Induced DNA Damage, Cell Cycle Arrest, Apoptosis, Inflammatory, Metabolic, and Oxidative Stress in HepG2 Cells

“…SIRT1 (sirtuin 1), an intracellular NAD-dependent deacetylase, is known to deacetylate target proteins and modulate the inflammatory response manifested by inflammatory cytokines [35,36]. In our study, we observed the activation of SIRT1 upon treatment with B(a)P. This could be the cell's survival response to B(a)P-induced NFκB activation.…”

“…AZD treatment decreased the expression of I-κB protein and decreased the translocation of NF-κB p65, indicating the anti-inflammatory action of AZD. SIRT1, a NAD-dependent deacetylase, functions as an intracellular regulatory protein and is known to regulate inflammation in various diseases [35,36]. Our results showed an increase in SIRT-1 expression after B(a)P treatment, which increased still further upon treatment with AZD (Figure 11D).…”