N‑acetyl cysteine inhibits the lipopolysaccharide‑induced inflammatory response in bone marrow mesenchymal stem cells by suppressing the TXNIP/NLRP3/IL‑1β signaling pathway.

Abstract

N-acetyl cysteine (NAC) has been used to inhibit lipopolysaccharide (LPS)-induced inflammation. However, the molecular mechanism underlying its anti-inflammatory effects remains to be elucidated. The present study aimed to determine the effect of NAC on the LPS-induced inflammatory response in bone marrow mesenchymal stem cells (BMSCs) and elucidate the underlying molecular mechanism. First, BMSCs were stimulated by LPS following pretreatment with NAC (0, 0.1, 0.5, 1 or 2 mM). A Cell Counting Kit 8 assay was used to determine the number of viable cells and 1 mM NAC was selected as the experimental concentration. Then, the secretion of inflammatory factors, including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α was evaluated by enzyme-linked immunosorbent assay. Finally, the expression levels of mRNA and proteins, including apoptosis-associated speck-like protein containing a CARD (ASC), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, thioredoxin-interacting protein (TXNIP), and thioredoxin (TRX), were evaluated by reverse transcription-quantitative PCR and western blot analysis, respectively. The results demonstrated that the secretion of inflammatory factors, which was increased by the administration of LPS, was reduced by pretreatment with NAC. Furthermore, NAC reduced the expression of ASC, NLRP3, caspase-1 and TXNIP, but enhanced that of TRX. To conclude, NAC had anti-inflammatory effects on LPS-stimulated BMSCs, which was closely associated with the TXNIP/NLRP3/IL-1β signaling pathway. Thus, NAC may be a promising treatment to attenuate the inflammatory response in LPS-induced BMSCs.