Sulfated non-anticoagulant heparin blocks Th2-induced asthma by modulating the IL-4/signal transducer and activator of transcription 6/Janus kinase 1 pathway

Journal of Translational Medicine
Mohamed A GhonimA Hamid Boulares

Abstract

The efficacy of heparins and low-MW-heparins (LMWH) against human asthma has been known for decades. However, the clinical utility of these compounds has been hampered by their anticoagulant properties. Much effort has been put into harnessing the anti-inflammatory properties of LMWH but none have been used as therapy for asthma. Sulfated-non-anticoagulant heparin (S-NACH) is an ultra-LMWH with no systemic anticoagulant effects. The present study explored the potential of S-NACH in blocking allergic asthma and examined the potential mechanism by which it exerts its effects. Acute and chronic ovalbumin-based mouse models of asthma, splenocytes, and a lung epithelial cell line were used. Mice were challenged with aerosolized ovalbumin and administered S-NACH or saline 30 min after each ovalbumin challenge. Sulfated-non-anticoagulant heparin administration in mice promoted a robust reduction in airway eosinophilia, mucus production, and airway hyperresponsiveness even after chronic repeated challenges with ovalbumin. Such effects were linked to suppression of Th2 cytokines IL-4/IL-5/IL-13/GM-CSF and ovalbumin-specific IgE without any effect on IFN-γ. S-NACH also reduced lung fibrosis in mice that were chronically-exposed to ovalbu...Continue Reading

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Citations

Nov 7, 2019·Current Opinion in Allergy and Clinical Immunology·Xuesong ChenEvan Li
Mar 7, 2020·Biomolecules & Therapeutics·Annamneedi Venkata PrakashTae Jin Kang
Aug 1, 2020·Frontiers in Pharmacology·Judith A VoynowApparao B Kummarapurugu

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Methods Mentioned

BETA
bronchoalveolar lavage
ELISA

Software Mentioned

GraphPad
Prism

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