STAT6 and Furin Are Successive Triggers for the Production of TGF-ß by T Cells.

Production of TGF-ß by T cells is key to various aspects of immune homeostasis, with defects in this process causing or aggravating immune-mediated disorders. The molecular mechanisms that lead to TGF-ß generation by T cells remain largely unknown. To address this issue, we take advantage of the fact that intestinal helminths stimulate Th2 cells besides triggering TGF-ß generation by T lymphocytes and regulate immune-mediated disorders. We show that the Th2 cell-inducing transcription factor STAT6 is necessary and sufficient for the expression of TGF-ß propeptide in T cells. STAT6 is also necessary for several helminth-triggered events in mice, such as TGF-ß-dependent suppression of alloreactive inflammation in graft-versus-host disease. Besides STAT6, helminth-induced secretion of active TGF-ß requires cleavage of propeptide by the endopeptidase furin. Thus, for the immune regulatory pathway necessary for TGF-ß production by T cells, our results support a two-step model, composed of STAT6 and furin.

Endoscopic Cyanoacrylate Glue Injection in Management of Gastric Variceal Bleeding: US Tertiary Care Center Experience.

BACKGROUND/AIMS: Although endoscopic cyanoacrylate glue injection (ECGI) is recommended as first-line treatment for bleeding gastric varices (GV) there is still limited experience with this method in the US. Our aim was to analyze our 10-year experience of ECGI for treatment and prophylaxis of gastric variceal bleeding. METHODS: Records of patients undergoing ECGI of GV at our US tertiary care center between 6/2005 and 5/2015 were reviewed. Assessed outcomes were primary hemostasis, early rebleeding during hospitalization, recurrent bleeding during follow-up, eradication and recurrence of GV. RESULTS: Prophylactic ECGI was performed in 16 patients with large GV. Eradication was achieved in 15 (94%). During the median follow-up of 27 (IQR 7-47) months, 4 patients (26.6%) had variceal bleeding; all were treated successfully with ECGI. Fifty-seven patients underwent ECGI for GV bleeding. Primary hemostasis was achieved in all. Early rebleeding occurred in 2 (3.5%) and durable hemostasis could not be achieved. Follow-up beyond initial hospitalization was available in 41 patients. Bleeding recurred in 8 (19.5%) patients during a median follow-up of 12 (IQR, 3-51) months. Eradication of GV was achieved in 92% of patients but recurrent varices were found in 44% during a median follow up period of 33 months. CONCLUSION: ECGI is effective in achieving hemostasis of bleeding GV and their eradication. Recurrent bleeding and recurrence of varices after complete obliteration however are not infrequent and continued surveillance is advisable.