Mechanism of Probiotic VSL#3 Inhibiting NF-κB and TNF-α on Colitis through TLR4-NF-κB Signal Pathway

Abstract

Background: We aimed to investigate the effect of probiotic VSL#3 on NF-κB and TNF-α in rats with colitis and the correlation with TLR4-NF-κB signal pathway.

Methods: Sixty Sprague Dawley (SD) rats were divided into the control, model and therapy groups (n=20) according to the random number table. Rats in the model and therapy groups were modeled for colitis, and rats in the therapy group were intragastrically administered with probiotic VSL#3. The expression of TLR4 and NF-κB protein, and the levels of NF-κB, TLR4, and TNF-α mRNA in the colon tissue were detected. The concentration of TNF-α in the serum after modeling but before intragastric administration (T0), 3d (T1) and 7d after intragastric administration (T2) was detected.

Results: The expression of TLR4 and NF-κB p65 protein, and the levels of TLR4, NF-κB, and TNF-α mRAN in the therapy group decreased (P < 0.001). At T0, T1, and T2, the concentration of TNF-α in the model and control groups increased (P < 0.001). TLR4 and NF-κB in the therapy group were positively correlated with TNF-α mRAN (P < 0.050).Conclusion: In conclusion, probiotic VSL#3 inhibits the expression of NF-κB and TNF-α in rats with colitis through TLR4-NF-κB signal pathway, so it is expected to be a first choice drug for the treatment of colitis.

Conclusion: In conclusion, probiotic VSL#3 inhibits the expression of NF-κB and TNF-α in rats with colitis through TLR4-NF-κB signal pathway, so it is expected to be a first choice drug for the treatment of colitis.

Keywords: NF-κB; Probiotics VSL#3; TLR4; TNF-α.

Fig. 1:

Detection results of TLR4 and NF-κB p65 protein expression The expression of TLR4 protein in the therapy group was (0.54±0.04), significantly lower than (0.82±0.07) in the model group (P < 0.001), but significantly higher than (0.08±0.02) in the control group (P < 0.001). The expression of NF-κB p65 protein in the therapy group was (0.92±0.07), significantly lower than (1.94±0.15) in the model group (P < 0.001), but significantly higher than (0.24±0.05) in the control group (P < 0.001)

Fig. 2:

Comparison of results of PCR The levels of TLR4, NF-κB and TNF-α mRAN in the therapy group were significantly lower than those in the model group, but higher than those in the control group. * indicates P < 0.001 compared with the model group. # indicates P < 0.001 compared with the therapy group

Fig. 3:

Correlation of TLR4 with TNF-α mRAN in therapy group According to Pearson correlation analysis in the therapy group, TLR4 was positively correlated with TNF-α mRAN (r = 0.619, P = 0.005)

Fig. 4:

Correlation of NF-κB with TNF-α mRAN in therapy group According to Pearson correlation analysis in the therapy group, NF-κB was positively correlated with TNF-α mRAN (r = 0.629, P = 0.004)

Fig. 5:

Comparison of concentration of TNF-α At T0, the concentration of TNF-α in the model and control groups was significantly higher than that in the control group. At T1 and T2, the concentration in the therapy group was significantly higher than that in the control group, but significantly lower than that in the model group. In the therapy group, the concentration at T0 was the highest, which at T1 was lower than that at T0 and which at T2 was lower than that at T1. * indicates P < 0.001 compared with the model group at T0. # indicates P < 0.001 compared with the model group at T1. △ indicates P < 0.001 compared with the model group at T2. ▽ indicates P < 0.001 compared with the therapy group at T0. □ indicates P < 0.001 compared with the therapy group at T1

Fig. 6:

Correlation of concentration of TNF-α with treatment time According to Spearman correlation coefficients, TNF-α was negatively correlated with treatment time (r=−0.938, P < 0.001, 95%CI: −0.964∼−0.897)