Role of ROCK/NF‑κB/AQP8 signaling in ethanol‑induced intestinal epithelial barrier dysfunction.

The present study aimed to investigate the signaling pathways and the underlying molecular mechanisms involved in ethanol‑induced intestinal epithelial barrier (IEB) dysfunction. Therefore, an in vitro experimental model of IEB was established using an ethanol‑treated Caco‑2 intestinal epithelial cell monolayer. The results confirmed that Rho‑associated kinases (ROCKs), namely ROCK1 and ROCK2, were involved in the underlying pathway of ethanol‑induced IEB dysfunction. Ethanol exposure significantly increased the expression of both ROCK isoforms and the activity of nuclear factor κB (NF‑κB). Furthermore, ROCK1‑ and ROCK2‑specific small interfering RNAs (siRNAs), and the NF‑κB inhibitor ammonium pyrrolidine dithiocarbamate partially inhibited transepithelial electrical resistance in Caco‑2 cells in an in vitro IEB model. In addition, ROCK1‑ and ROCK2‑specific siRNAs inhibited the activity of NF‑κB, thereby downregulating the expression of aquaporin 8 (AQP8). Taken together, the results of the present study suggested that ROCK1/ROCK2‑mediated activation of NF‑κB and upregulation of AQP8 expression levels may represent a novel mechanism of ethanol‑induced impairment of IEB function.