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Molecular Medicine

, Volume 16, Issue 9–10, pp 343–351 | Cite as

Immunomodulatory Drugs Regulate HMGB1 Release from Activated Human Monocytes

  • Hanna Schierbeck
  • Heidi Wähämaa
  • Ulf Andersson
  • Helena Erlandsson Harris
Research Article

Abstract

Several HMGBl-specific antagonists have provided beneficial results in multiple models of inflammatory disease-preclinical trials including arthritis. Since no HMGB1-specific targeted therapy has yet reached the clinic, we have performed in vitro studies to investigate whether any of a selection of well-established antirheumatic drugs inhibit HMGB1 release as part of its mode of action. Freshly purified peripheral blood monocytes from healthy donors were stimulated in cultures with LPS and IFNγ to cause HMGB1 and TNF release detected in ELISPOT assays. Effects on the secretion were assessed in cultures supplemented with dexamethasone, cortisone, chloroquine, gold sodium thiomalate, methotrexate, colchicine, etanercept or anakinra. Pharmacologically relevant doses of dexamethasone, gold sodium thiomalate and chloroquine inhibited the extracellular release of HMGB1 in a dose-dependent mode. Immunostaining demonstrated that dexamethasone caused intracellular HMGB1 retention. No effects on HMGB1 secretion were observed in cultures with activated monocytes by any of the other studied agents. TNF production in LPS/IFNγ-activated monocytes was readily downregulated by dexamethasone and, to some extent, by chloroquine and etanercept. We conclude that dexamethasone, gold sodium thiomalate and chloroquine share a capacity to inhibit HMGB1 release from activated monocytes.

Notes

Acknowledgments

Financial support was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Association against Rheumatism, the Swedish Medical Research Council, the Freemason Lodge Barnhuset in Stockholm, and King Gustaf V’s Foundation.

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Copyright information

© The Feinstein Institute for Medical Research 2010

Authors and Affiliations

  • Hanna Schierbeck
    • 1
    • 3
  • Heidi Wähämaa
    • 1
    • 3
  • Ulf Andersson
    • 1
    • 3
  • Helena Erlandsson Harris
    • 2
    • 3
  1. 1.Department of Women’s and Children’s Health, Pediatric UnitKarolinska Institutet/Karolinska University Hospital Q1:02StockholmSweden
  2. 2.Department of Medicine, Rheumatology UnitKarolinska InstitutetStockholmSweden
  3. 3.Rheumatology Research Laboratory, Center for Molecular Medicine, Karolinska InstitutetKarolinska University HospitalStockholmSweden

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