Antiproliferative-antiinflammatory effects of methotrexate and sex hormones on cultured differentiating myeloid monocytic cells (THP-1)

Maurizio Cutolo, Alberto Sulli, Chiara Craviotto, Lamberto Felli, Carmen Pizzorni, Bruno Seriolo, Barbara Villaggio

Research output: Contribution to journalArticle

Abstract

Methotrexate (MTX) is believed to exert both antiproliferative and antiinflammatory effects in a dose-related manner in a majority of rheumatoid arthritis (RA) patients along with an abrupt flare of the disease after drug discontinuation. To investigate the antiproliferative and antiinflammatory actions of MTX and the combined action of sex hormones, we evaluated these effects in differentiated monocytic myeloid cells (THP-1) prestimulated with testosterone (T) or 17-β estradiol (E2). The effects of MTX and T combined treatment (T/MTX) on THP-1 cells showed a significant inhibition of cell proliferation when compared with E2/MTX- treated cells or controls: 53% at 72 h versus E2-treated cells; 58% at 96 h versus E2-treated cells; and 41% versus controls, respectively. Bax and Fas CD95 expression was found increased in T-treated cells: 14% T at 48 h vs. E2-treated cells and controls; 45% T at 72 h versus E2-treated cells and controls; 97% at 96 h versus E2-treated cells and 37% versus controls for Bax: 33%, 41%, and 42% T versus E2-treated cells for Fas. Moreover, a significant decrease of IL-12 levels in T/MTX treated cells was found at any time when compared to E2-treated cells. In summary, the association of testosterone and MTX compared to MTX alone suggests possible synergistic actions. Therefore, the enhancing antiinflammatory effects exerted by androgens might represent a further explanation for the reduced frequency of inflammatory diseases in male subjects.

Original languageEnglish
Pages (from-to)232-237
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume966
Publication statusPublished - 2002

Keywords

  • Androgens
  • Antiinflammatory effects
  • Antiproliferative effects
  • Estrogens
  • Methotrexate
  • Myeloid monocytic cells
  • Sex hormones

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Cutolo, M., Sulli, A., Craviotto, C., Felli, L., Pizzorni, C., Seriolo, B., & Villaggio, B. (2002). Antiproliferative-antiinflammatory effects of methotrexate and sex hormones on cultured differentiating myeloid monocytic cells (THP-1). Annals of the New York Academy of Sciences, 966, 232-237.