Effects of NF-κB p65 antisense oligonucletide on the expression of cytokines and NF-κB in colonic intestinal mucosa of mice with TNBS-induced colitis

Abstract

AIM: To evaluate the effects of nuclear factor kappa B (NF-κB) p65 antisense oligonucleotide on the inflammation, expression of cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (IL-1β, IL-10) and NF-κB in colonic intestinal mucosa of mice with trinitrobenzene sulfonic acid-induced colitis. METHODS: Fifty BALB/c mice were randomly divided into model control group (UC), antisense oligonucleotide treatment group (ASOND), missense oligonucleotide treatment group (MSOND), and sense oligonucleotide treatment group (SOND). Experimental colitis was induced by trinitrobenzene sulfonic acid (TNBS)/ethanol enema. Twenty-four hours after modeling, the mice in the ASOND, MSODN and SODN groups were administered with the corresponding oligonucleotides, Inflammatory scores and mucosal morphological changes were evaluated under light microscope, The leves of TNF-α, IL-1β, IL-10 and NF-κB were determined by immunohistochemistry. RESULTS: The inflammatory scores in the ASOND group decreased as compared with those in the VC, MSOND and SOND group (all P＜0.05). The mucosal levels of TNF-α, IL-1β and NF-κB expression in the ASOND group were significantly lower than those in the VC, MSOND and SOND groups (82.68±14.30 vs 168.48±11.89, 166.49±11.63, 176.49±12.33, P＜0.05; 42.42±5.77 vs 168.48±11.89, 120.43±28.21, 131.43±30.601, P＜0.01; 62.66±11.32 vs 158.38±12.49, 161.09±12.73, 168.64±11.83, P＜0.01), while IL-10 levels were higher (146.68±6.02 vs 62.50±11.57, 58.44±10.92, 54.24±10.64, P＜0.01). CONCLUSION: ASOND can attenuate the inflammatory degree in mice with experimental colitis and effectively down-regulates TNF-α, IL-1β and NF-κB expression while up-regulates IL-10 secretion.