BACKGROUND: Inflammatory bowel disease (IBD), a chronic inflammation of the gastrointestinal tract, is characterized by a deregulation of the mucosal immune system and resistance of activated T cells to apoptosis. Current therapeutics show limited efficacy and potential toxicity; therefore there is a need for novel approaches for the treatment of IBD. L-cysteine was examined for its ability to reduce colitis symptoms and modulate local gene expression in a DSS-induced porcine model of colitis. METHODS: Colitis was induced via intra-gastric infusion of dextran sodium sulfate (DSS), followed by the administration of L-cysteine or saline. Clinical signs, morphological measurements, histology and gut permeability were assessed for the prognosis of colitis. Local tissue production of cytokines and gene expression in the colon were analyzed by ELISA and real-time RT-PCR. RESULTS: L-cysteine supplementation attenuated DSS-induced weight loss and intestinal permeability, reduced local chemokine expression and neutrophil influx, and markedly improved colon histology. Furthermore, cysteine significantly reduced the expression of pro-inflammatory cytokines, including TNF-alpha, IL-6, IL-12p40, IL-1beta, and resulted in increased expression of the apoptosis initiator caspase-8 and decreased expression of the pro-survival genes cFLIP and Bcl-xL. CONCLUSIONS AND GENERAL SIGNIFICANCE: These results suggest that L-cysteine administration aids in restoring gut immune homeostasis by attenuating inflammatory responses and restoring susceptibility of activated immune cells to apoptosis, and that cysteine supplementation may be a novel therapeutic strategy for the treatment of IBD.
BACKGROUND:Inflammatory bowel disease (IBD), a chronic inflammation of the gastrointestinal tract, is characterized by a deregulation of the mucosal immune system and resistance of activated T cells to apoptosis. Current therapeutics show limited efficacy and potential toxicity; therefore there is a need for novel approaches for the treatment of IBD. L-cysteine was examined for its ability to reduce colitis symptoms and modulate local gene expression in a DSS-induced porcine model of colitis. METHODS:Colitis was induced via intra-gastric infusion of dextran sodium sulfate (DSS), followed by the administration of L-cysteine or saline. Clinical signs, morphological measurements, histology and gut permeability were assessed for the prognosis of colitis. Local tissue production of cytokines and gene expression in the colon were analyzed by ELISA and real-time RT-PCR. RESULTS:L-cysteine supplementation attenuated DSS-induced weight loss and intestinal permeability, reduced local chemokine expression and neutrophil influx, and markedly improved colon histology. Furthermore, cysteine significantly reduced the expression of pro-inflammatory cytokines, including TNF-alpha, IL-6, IL-12p40, IL-1beta, and resulted in increased expression of the apoptosis initiator caspase-8 and decreased expression of the pro-survival genes cFLIP and Bcl-xL. CONCLUSIONS AND GENERAL SIGNIFICANCE: These results suggest that L-cysteine administration aids in restoring gut immune homeostasis by attenuating inflammatory responses and restoring susceptibility of activated immune cells to apoptosis, and that cysteine supplementation may be a novel therapeutic strategy for the treatment of IBD.
Authors: M Stojanović; D Todorović; Lj Šćepanović; D Mitrović; S Borozan; V Dragutinović; M Labudović-Borović; D Krstić; M Čolović; D Djuric Journal: Mol Cell Biochem Date: 2018-02-08 Impact factor: 3.396
Authors: Gang Zhao; Xin Wei; Jianbo Wu; Derrick D Eichele; Subodh M Lele; Libin Yang; Fan Zhang; Dong Wang Journal: Pharm Res Date: 2019-03-11 Impact factor: 4.200
Authors: S Hasegawa; T Ichiyama; I Sonaka; A Ohsaki; S Okada; H Wakiguchi; K Kudo; S Kittaka; M Hara; S Furukawa Journal: Clin Exp Immunol Date: 2012-02 Impact factor: 4.330
Authors: Laxmi Sunuwar; Michal Medini; Limor Cohen; Israel Sekler; Michal Hershfinkel Journal: Philos Trans R Soc Lond B Biol Sci Date: 2016-08-05 Impact factor: 6.237