Inhibiting Rac1 signaling alleviates DSS-induced colitis by improving inflammatory response and intestinal permeability.

[BACKGROUND] This study aimed to explore the regulation of Ras-related C3 botulinum toxin substrate1 (Rac1) on the intestinal barrier function in colitis and explore its molecular mechanism of regulation on tight junctions.

[METHODS] A dextran sulfate sodium (DSS)-induced colitis mouse model was used. The diseases activity index (DAI) was calculated daily. Epithelial permeability was measured. Colon sections were stained with hematoxylin and eosin, and the histological severity was analysed. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyse the messenger ribonucleic acid (mRNA) level of Rac1, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), and occludin in the colon. Western blot was used to detect occludin protein expression.

[RESULTS] Colitis mice showed increased DAI and histological scores, reduced colon length, and impaired epithelial permeability, which were significantly alleviated by the administration of Rac1 inhibitor NSC23766. The level of inflammatory genes including interleukin 6 (IL-6), myeloperoxidase and NOX1 in the colon tissue were elevated in colitis mice, while the administration of NSC23766 remarkably reduced the expression of these genes. Western blot analysis showed that the occludin protein level was suppressed by DSS, while NSC23766 treatment restored the expression of occludin in DSS mice.

[CONCLUSIONS] Rac1 inhibitor NSC23766 attenuates symptoms, colonic inflammation, and intestinal permeability in a DSS-induced colitis model. These effects may be attributed to the suppression of inflammatory responses and DSS-induced damage of intestinal integrity.