Sahar Tahvili1, Basira Zandieh2, Zahra Amirghofran1,3. 1. Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Department of Dermatology, Shiraz University of Medical Sciences, Shiraz, Iran. 3. Department of Autoimmune Disease Research Center and Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Abstract
BACKGROUND: Fumaric acid esters such as dimethyl fumarate (DMF) have proven to be effective in the treatment of psoriasis. OBJECTIVES: In view of the role of Th17 in the pathogenesis of psoriasis, the present study was conducted to investigate the effects of DMF on Th1, Th2, and Th17 responses in patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from psoriasis patients and healthy individuals and were cultured in the presence or absence of phytohemagglutinin and DMF. The cell supernatants were removed to measure cytokine secretion, and the lymphocytes were used for real-time polymerase chain reaction to establish gene expression. RESULTS: An increase in gene expression of interferon-γ (IFN-γ), as a marker for Th1 activity, and interleukin-17 (IL-17), granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-22 representing the Th17 subset in the PBMCs of patients in comparison with those of control subjects was observed. Culture of PBMCs from psoriasis patients and controls in the presence of DMF decreased IFN-γ and increased IL-4 gene expression in both groups. Treatment with DMF could significantly decrease IL-17, GM-CSF, and IL-22 mRNA levels in the PBMCs of patients. Decreased release of IFN-γ and GM-CSF cytokine secretion after DMF treatment was also observed in PBMC cultures of patients and controls. CONCLUSIONS: These data show the effectiveness of DMF in modulating Th17 cells in addition to Th1/Th2 cells and reflect one of the underlying mechanisms of action of DMF in psoriasis. These findings may also support the possible benefits of using fumarate in the treatment of other autoimmune diseases in the pathogeneses of which Th1 and Th17 cells play major roles.
BACKGROUND:Fumaric acid esters such as dimethyl fumarate (DMF) have proven to be effective in the treatment of psoriasis. OBJECTIVES: In view of the role of Th17 in the pathogenesis of psoriasis, the present study was conducted to investigate the effects of DMF on Th1, Th2, and Th17 responses in patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from psoriasispatients and healthy individuals and were cultured in the presence or absence of phytohemagglutinin and DMF. The cell supernatants were removed to measure cytokine secretion, and the lymphocytes were used for real-time polymerase chain reaction to establish gene expression. RESULTS: An increase in gene expression of interferon-γ (IFN-γ), as a marker for Th1 activity, and interleukin-17 (IL-17), granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-22 representing the Th17 subset in the PBMCs of patients in comparison with those of control subjects was observed. Culture of PBMCs from psoriasispatients and controls in the presence of DMF decreased IFN-γ and increased IL-4 gene expression in both groups. Treatment with DMF could significantly decrease IL-17, GM-CSF, and IL-22 mRNA levels in the PBMCs of patients. Decreased release of IFN-γ and GM-CSF cytokine secretion after DMF treatment was also observed in PBMC cultures of patients and controls. CONCLUSIONS: These data show the effectiveness of DMF in modulating Th17 cells in addition to Th1/Th2 cells and reflect one of the underlying mechanisms of action of DMF in psoriasis. These findings may also support the possible benefits of using fumarate in the treatment of other autoimmune diseases in the pathogeneses of which Th1 and Th17 cells play major roles.
Authors: Paul Sator; Robert Loewe; Omid Zamani; Gregor Holzer; Peter Wolf; Alexander Mlynek; Thomas Berger; Leo Richter; Elisabeth Schuller Journal: Wien Klin Wochenschr Date: 2019-10-07 Impact factor: 1.704
Authors: Larissa Staurengo-Ferrari; Stephanie Badaro-Garcia; Miriam S N Hohmann; Marília F Manchope; Tiago H Zaninelli; Rubia Casagrande; Waldiceu A Verri Journal: Front Pharmacol Date: 2019-01-11 Impact factor: 5.810
Authors: Arie R Gafson; Kicheol Kim; Maria T Cencioni; Wim van Hecke; Richard Nicholas; Sergio E Baranzini; Paul M Matthews Journal: Neurol Neuroimmunol Neuroinflamm Date: 2018-06-12