title: Triptolide induces suppressor of cytokine signaling-3 expression and promotes lamina propria mononuclear cells apoptosis in Crohn's colitis.
abstract: BACKGROUND
  IL-6/STAT3/SOCS3 signaling pathway plays an important role in the pathogenesis of Crohn's disease by induction of the antiapoptotic factors Bcl-2 and Bcl-xl in lamina propria mononuclear cells (LPMCs). We previously reported that triptolide showed therapeutic activity in mouse colitis by mechanisms involving suppression of IL-6 trans-signaling. IL-10 gene-deficient mice with established colitis were used for the experiments with triptolide administration.
  
  
  METHODS
  This study further investigates the mechanism by which triptolide attenuates Crohn's colitis. IL-10 gene-deficient mice (IL-10(-)/(-)) of 10-12weeks with established colitis were used for the experiments with chronic triptolide administration. Apoptosis of lamina propria mononuclear cells (LPMCs) were measured by flow cytometry. SOCS, Bcl-2, Bcl-xl and Bax were determined by Western blot. Furthermore, an in vitro study was performed by using cultured intestine from CD patients to observe the direct effects of triptolide.
  
  
  RESULTS
  Our data indicated triptolide promoted apoptosis in LPMCs in vivo. Interestingly, triptolide significantly induced the apoptosis of LP-CD4-positive but not LP-CD4-negative cells. Triptolide significantly induced SOCS3 protein and reduced STAT3 target anti-apoptotic genes Bcl-2 and Bcl-xl in LPMCs. The results were confirmed by an in vitro study using colonic explants cultured with triptolide.
  
  
  CONCLUSIONS
  Our results indicated that triptolide therapy may restore the homeostatic balance of LP-T cell apoptosis within the gut, and demonstrate a novel mechanism of action of triptolide therapy mediated through regulation IL-6/STAT3/SOCS3 signaling pathway.
authors: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.
authors: Yi
authors: Y
authors: Li
authors: Yun
authors: Y
authors: Tian
authors: Weiming
authors: W
authors: Zhu
authors: Jianfeng
authors: J
authors: Gong
authors: Wei
authors: W
authors: Zhang
authors: Chao
authors: C
authors: Yu
authors: Lili
authors: L
authors: Gu
authors: Ning
authors: N
authors: Li
authors: Jieshou
authors: J
authors: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000166:cytology* / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C494812:Bcl2l1 protein, mouse; D004224:Diterpenes; D004852:Epoxy Compounds; C556062:IL10 protein, mouse; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051020:bcl-X Protein; D016753:Interleukin-10; C001899:triptolide; D012319:RNA Polymerase II