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Allergy. 2015 Sep;70(9):1130-8. doi: 10.1111/all.12651. Epub 2015 Jun 2.

2-Chloroacetamidine, a novel immunomodulator, suppresses antigen-induced mouse airway inflammation.

Author information

1
The Hospital for Sick Children Research Institute, Neuroscience and Mental Health, University of Toronto, Toronto, ON, Canada.
2
Department of Neurology and Center for Neuroimmunology, University of Alabama at Birmingham, Birmingham, AL, USA.
3
Birmingham VA Medical Center, Birmingham, AL, USA.

Abstract

BACKGROUND:

Citrullination is a presently under-recognized posttranslational protein modification catalyzed by PAD enzymes. Immune responses to citrullinated neo-epitopes are identified in a growing number of inflammatory and autoimmune diseases. However, the involvement of hypercitrullination in the pathogenesis of bronchial asthma is still unknown.

METHODS:

As main experimental tool, we examined the effect of 2-chloroacetamidine (2CA), a PAD enzyme inhibitor, on OVA-immunized and airway-challenged BALB/c mice; a commonly used model of allergic airway inflammation. We also measured the effect of 2CA on ex vivo lymphocytes and cell lines.

RESULTS:

In vivo, 2CA dramatically suppressed lung tissue hypercitrullination, inflammatory cell recruitment, and airway-Th2 cytokine secretion. 2CA also suppressed systemic OVA-specific and total IgE production dramatically, effectively preventing de novo and diminishing established disease without measurably impacting general immunocompetence. In vitro, 2CA markedly inhibited the proliferation of mouse and human T cells with cell cycle block and apoptosis during a limited, postactivation phase.

CONCLUSIONS:

2CA acts as narrow-spectrum immunosuppressant that selectively targets lymphocyte populations involved in active inflammatory tissue lesions. If hypercitrullination is generated in patients with asthma, 2CA may represent a novel disease modulator for human asthmatics/allergic diseases.

KEYWORDS:

T cell; animal model; asthma; protein citrullination

PMID:
25969859
DOI:
10.1111/all.12651
[Indexed for MEDLINE]

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