title: 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.
abstract: 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.
authors: Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100071, China.
authors: Yong-Jian
authors: YJ
authors: Gao
authors: Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100071, China. qjiaming57@gmail.com.
authors: Feng
authors: F
authors: Zhu
authors: Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100071, China.
authors: Jia-Ming
authors: JM
authors: Qian
authors: Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100071, China.
authors: Jia-Yuan
authors: JY
authors: Dai
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D015153:Blotting, Western; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D007150:Immunohistochemistry; D056747:Immunomodulation / Q000187:drug effects; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D020825:T-Box Domain Proteins / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; D011134:Polysaccharides; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase
keywords: 2,4,6-trinitrobenzene sulfonic acid-induced colitis; Astragalus polysaccharides; Chinese medicine; GATA-3; T-bet; rats