Therapeutic and immunoregulatory effect of GATA-binding protein-3/T-box expressed in T-cells ratio of astragalus polysaccharides on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats.

OBJECTIVE

To analyze the immunological characteristics of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model and examine the therapeutic effects and mechanisms of Astragalus polysaccharides (APS) treatment.

METHODS

Thirty-two male specific pathogen free Spragne-Dawley rats were randomly equally assigned to four groups: control, TNBS, APS and prednisone groups. Experimental colitis was induced by enema administration of TNBS. Then rats were treated with APS (0.5 g•kg-1•day-1, once daily) or prednisone (1.0 mg•kg-1•day-1, once daily) by gavage for 14 days. Macroscopic lesion and histological damage were determined, and activity of myeloperoxidase (MPO) was measured in the colonic tissues. Expressions of T-box expressed in T-cells (T-bet) and GATA-binding protein-3 (GATA-3) were determined by immunohistochemistry analysis and western blot.

RESULTS

Both macroscopic lesion and histological colonic damage induced by TNBS were reduced by APS and prednisone treatment. These were accompanied by significant attenuation of MPO activity (P=0.03). TNBS intervention enhanced the expression of both GATA-3 and T-bet, but the expression of T-bet was significantly enhanced than that of GATA-3, resulting in significant reduction of GATA-3/T-bet ratio (P=0.025). APS administration enhanced the expression of T-bet (P=0.04) and GATA-3 (P=0.019) in comparison to TNBS group, and resulting in an up-regulated GATA-3/T-bet ratio. Prednisone treatment inhibited both expressions; however it also resulted in up-regulation of the GATA-3/T-bet ratio.

CONCLUSIONS

These results demonstrated that APS exerted a beneficial immune regulatory effect on experimental colitis. It promoted the expression of T helper cell 1 (Th1) and T helper cell 2 (Th2) specific transcription factors but ultimately favor a shift toward Th2 phenotype, suggesting that APS possessed therapeutic potential in experimental colitis.