title: Folinic acid antagonizes methotrexate-induced differentiation of monocyte progenitors.
abstract: OBJECTIVE
  The anti-inflammatory action of low-dose methoxetrate (MTX) in the treatment of rheumatoid arthritis (RA) appears to be partially impaired by folate supplementation. Here we investigated whether a folate excess impairs monocyte differentiation, a putative anti-inflammatory action of low-dose MTX.
  
  
  METHODS
  Monocyte differentiation of U937 promonocytic cells was assessed by CD11b and CD14 immunostaining and fluorescent absorbent cell sorting (FACS) analysis. Cell proliferation and viability were determined by cell counts and trypan-blue staining, respectively. Nuclear apoptosis was assessed by 7-actinomycin staining. Cells were treated with 10(-10)-10(-6) M MTX in the presence or absence of folinic acid. Exposure to 1,25-OH-vitamine D(3) and TGF-beta served as a positive control of monocyte differentiation in U937 cells.
  
  
  RESULTS
  Low-dose MTX-induced monocyte differentiation was marginal when compared with 1,25-OH-D(3) + TGF-beta treatment. Low-dose MTX inhibited cell proliferation, induced apoptosis, and reduced cell viability. All the antiproliferative, cytotoxic, and monocyte differentiating effects of MTX were completely reversed by folinic acid.
  
  
  CONCLUSIONS
  Monocyte differentiation is part of the folate-dependent MTX actions.
authors.affiliation: Medizinische Klinik III, Klinikum der Johann Wolfgang, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt/M., Germany. B.Moeller@em.uni-frankfurt.de
authors.forename: Burkhard
authors.initials: B
authors.lastname: Möller
authors.forename: Natasa
authors.initials: N
authors.lastname: Kukoc-Zivojnov
authors.forename: Stella
authors.initials: S
authors.lastname: Okamgba
authors.forename: Uta
authors.initials: U
authors.lastname: Kessler
authors.forename: Elena
authors.initials: E
authors.lastname: Puccetti
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Kaltwasser
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Martin
authors.initials: M
authors.lastname: Ruthardt
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis; D018845:CD11 Antigens / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005434:Flow Cytometry; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D018501:Antirheumatic Agents; D018845:CD11 Antigens; D018950:Lipopolysaccharide Receptors; D002117:Calcitriol; D002955:Leucovorin; D008727:Methotrexate