Premium
2‐Chloroacetamidine, a novel immunomodulator, suppresses antigen‐induced mouse airway inflammation
Author(s) -
Maezawa Y.,
Paltser G.,
Tsui H.,
Cheung R.,
Wu P.,
Nicholas A. P.,
Dosch H.M.
Publication year - 2015
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12651
Subject(s) - immunology , immune system , inflammation , medicine , immunoglobulin e , in vivo , pathogenesis , allergy , cytokine , antigen , biology , antibody , microbiology and biotechnology
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 (2 CA ), 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 2 CA on ex vivo lymphocytes and cell lines. Results In vivo, 2 CA dramatically suppressed lung tissue hypercitrullination, inflammatory cell recruitment, and airway‐Th2 cytokine secretion. 2 CA 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 , 2 CA markedly inhibited the proliferation of mouse and human T cells with cell cycle block and apoptosis during a limited, postactivation phase. Conclusions 2 CA acts as narrow‐spectrum immunosuppressant that selectively targets lymphocyte populations involved in active inflammatory tissue lesions. If hypercitrullination is generated in patients with asthma, 2 CA may represent a novel disease modulator for human asthmatics/allergic diseases.