Arsenic trioxide alleviates airway hyperresponsiveness and eosinophilia in a murine model of asthma.
Asthma is one of the most common chronic airway inflammatory diseases. The clinical hallmarks of asthma include elevated serum levels of immunoglobulin E (IgE), eosinophilic inflammation and airway hyper-responsiveness (AHR). Arsenic trioxide (As2O3) is considered a carcinogen; however, it has also been used to treat diseases, such as syphilis, in traditional Chinese and Western medicine. Today, As2O3 is used as one of the standard therapies for acute promyelocytic leukemia (APL). Previous studies have indicated that As2O3 can induce apoptosis in eosinophils. However, the effect of As2O3 on asthma has not been investigated. We used ovalbumin (OVA)-immunized mice as a model for asthma and treated mice with As2O3 at doses of 2.5 and 5 mg/kg. The mice were then monitored for OVA-specific IgE production, airway inflammatory cell infiltration and AHR. We found that administration of As2O3 in OVA-immunized mice abrogated airway eosinophil recruitment by downregulating eotaxin expression but did not alter serum IgE or IL-5 levels in bronchoalveolar lavage fluid (BALF). Furthermore, the development of AHR and cellular infiltration into the airway were reduced by treating mice with As2O3. In vitro data suggested that low concentrations of As2O3 could induce only a small degree of apoptosis in primary pulmonary cells but could significantly inhibit the secretion of eotaxin by these cells. These results indicate that the administration of As2O3 to OVA-immunized mice can suppress lung allergic inflammatory responses. As2O3 might therefore have therapeutic potential in treating allergic airway inflammatory diseases.
Chu
Kuan-Hua
KH
Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan.
Lee
Chen-Chen
CC
Hsin
Shao-Chi
SC
Cai
Bao-Chang
BC
Wang
Jin-Hong
JH
Chiang
Bor-Luen
BL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010087:Oxides / Q000627:therapeutic use*
D001152:Arsenicals; D015848:Interleukin-5; D010087:Oxides; D007073:Immunoglobulin E; D000077237:Arsenic Trioxide