Dexmedetomidine reduces dextran sulfate sodium (DSS)-induced NCM460 cell inflammation and barrier damage by inhibiting RhoA/ROCK signaling pathway

Allergol Immunopathol (Madr). 2022 May 1;50(3):85-92. doi: 10.15586/aei.v50i3.569. eCollection 2022.

Abstract

Objective: This study investigated the role of dexmedetomidine (DEX) in dextran sulfate sodium (DSS)-induced NCM460 cells.

Material and methods: The viability and apoptosis of NCM460 cells treated with DEX with or without DSS were detected by CCK-8 and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. The level of inflammatory factors and expression of inflammation-related proteins, tight junction proteins and Ras homolog gene family, member A/Rho-associated coiled-coil containing protein kinase (RhoA/ROCK) signaling-related proteins in NCM460 cells treated with DEX and/or U46619 (RhoA/ROCK agonist) and/or DSS were detected by the respective enzyme-linked immunosorbent assay (ELISA) kits and Western blot analysis. The permeability of NCM460 monolayers was examined with transepithelial electrical resistance (TEER) assay.

Results: DEX had no effect on NCM460 cell viability. However, DEX improved the viability and barrier damage and suppressed the apoptosis and inflammation of DSS-induced NCM460 cells. Correspondingly, the expression of inflammation-related proteins was reduced and the expression of tight junction proteins was increased in DSS-induced NCM460 cells after treatment with DEX. In addition, RhoA/ROCK signaling was activated in NCM460 cells induced by DSS, which was suppressed by DEX. The protective effects of DEX on DSS-indued NCM460 cells were reversed by U46619.

Conclusion: DEX improved viability and barrier damage while suppressed apoptosis and inflammation in DSS-indued NCM460 cells by inhibiting RhoA/ROCK signaling pathway.

Keywords: RhoA/ROCK signaling pathway; barrier damage; dexmedetomidine; inflammation; ulcerative colitis.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / metabolism
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Dexmedetomidine* / pharmacology
  • Dexmedetomidine* / therapeutic use
  • Dextran Sulfate / pharmacology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Signal Transduction
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism
  • rho-Associated Kinases / pharmacology
  • rhoA GTP-Binding Protein / metabolism
  • rhoA GTP-Binding Protein / pharmacology

Substances

  • RHOA protein, human
  • Dexmedetomidine
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Dextran Sulfate
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein