2-Chloroacetamidine, a novel immunomodulator, suppresses antigen-induced mouse airway inflammation.
Allergy
; 70(9): 1130-8, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-25969859
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Amidinas
/
Fatores Imunológicos
/
Imunossupressores
/
Antígenos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Allergy
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Canadá