Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation.

Abstract

RATIONALE:

Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites.

OBJECTIVES:

To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice.

METHODS:

Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured.

MEASUREMENTS AND MAIN RESULTS:

Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo.

CONCLUSIONS:

Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans.

• Authors: Christopher D Lucas, David A Dorward, Sidharth Sharma, Jillian Rennie, Jennifer M Felton, Ana L Alessandri, Rodger Duffin, Jurgen Schwarze, Christopher Haslett, Adriano G Rossi
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 191 Issue 6 Pg. 626-36 (Mar 15 2015) ISSN: 1535-4970 [Electronic] United States
• PMID: 25629436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavanones
• Ovalbumin
• wogonin

Topics

• Animals
• Apoptosis (drug effects)
• Bronchoalveolar Lavage
• Eosinophils (cytology, drug effects)
• Female
• Flavanones (pharmacology)
• Flow Cytometry
• Humans
• Hypersensitivity (physiopathology)
• In Vitro Techniques
• Inflammation
• Mice
• Mice, Inbred BALB C
• Ovalbumin (immunology)