Folinic acid antagonizes methotrexate-induced differentiation of monocyte progenitors.

Möller, Burkhard, Kukoc-Zivojnov, Natasa, Okamgba, Stella, Kessler, Uta, Puccetti, Elena, Ottmann, Oliver G. ORCID: https://orcid.org/0000-0001-9559-1330, Kaltwasser, Joachim P., Hoelzer, Dieter and Ruthardt, Martin ORCID: https://orcid.org/0000-0003-1021-3811 2002. Folinic acid antagonizes methotrexate-induced differentiation of monocyte progenitors. Rheumatology International 22 , 60–67. 10.1007/s00296-002-0188-9

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Springer
ISSN:	0172-8172
Date of Acceptance:	2 February 2002
Last Modified:	29 Feb 2024 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/166053

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