title: The effect of dimethyl fumarate on gene expression and the level of cytokines related to different T helper cell subsets in peripheral blood mononuclear cells of patients with psoriasis.
abstract: BACKGROUND
  Fumaric acid esters such as dimethyl fumarate (DMF) have proven to be effective in the treatment of psoriasis.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Sahar
authors.initials: S
authors.lastname: Tahvili
authors.affiliation: Department of Dermatology, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Basira
authors.initials: B
authors.lastname: Zandieh
authors.affiliation: Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.|Department of Autoimmune Disease Research Center and Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Amirghofran
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D003879:Dermatologic Agents / Q000494:pharmacology*; D000069462:Dimethyl Fumarate / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects*; D018417:Th1 Cells / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D003879:Dermatologic Agents; D000069462:Dimethyl Fumarate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D020381:Interleukin-17; D015847:Interleukin-4; D007378:Interleukins; D012333:RNA, Messenger; D000097043:Interleukin-22