Silencing IL-23 expression by a small hairpin RNA protects against asthma in mice

EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 43, No. 4, 197-204, April 2011

Silencing IL-23 expression by a small hairpin RNA protects against asthma in mice

Yanchun Li1*, Meng Sun2*, Huanji Cheng1, Shanyu Li1, Li Liu1, Hongmei Qiao1, Shucheng Hua3,4 and Jirong Lu1,4

1Department of PediatricsThe First Hospital of Jilin University Changchun, Jilin, 130021, China

2Qingdao Women and Children Medical Care Center Qingdao, Shandong, 266011, China

3Department of Respiratory Medicine The First Hospital of Jilin University Changchun, Jilin, 130021, China

4Corresponding authors: Tel: [phone];

Fax, 86-043185654528; E-mail, [email protected] (S. Hua) Tel, 86-13504705565; Fax, 86-043185654528;

Email, [email protected] (J. Lu)*These authors contributed equally to this work.

DOI 10.3858/emm.2011.43.4.024

Accepted 2 March 2011 Available Online 4 March 2011

Abbreviations: Alum, aluminum hydroxide; BALF, bronchoalveolar lavage fluid; COPD, chronic obstructive pulmonary disease; CIA, collagen-induced arthritis; DAB, diaminobenzidine; EAE, encephalomyelitis; HE, hematoxylin and eosin; IBD, inflammatory bowel disease; OVA, ovalbumin; RT-PCR, reverse transcription polymerase chain reaction; RNAi, RNA interference; VCAM-1, vascular cell adhesion molecule; VLA4, very late antigen-4

Abstract

To determine the impact of IL-23 knockdown by RNA interference on the development and severity of oval-bumin (OVA)-induced asthmatic inflammation, and the potential mechanisms in mice, the IL-23-specific RNAi-expressing pSRZsi-IL-23p19 plasmid was constructed and inhaled into OVA-sensitized mice before each challenge, as compared with that of control mice treated with alum or budesonide. Inhalation of the pSRZsi-IL-23p19, significantly reduced the levels of OVA-challenge induced IL-23 in the lung tissues by nearly 75%, determined by RT-PCR. In addition, knockdown of IL-23 expression dramatically reduced the numbers of eosinophils and neutrophils in BALF and mitigated inflammation in the lungs of asthmatic mice. Furthermore, knockdown of IL-23 expression significantly decreased the levels of serum IgE, IL-23,

IL-17, and IL-4, but not IFN, and its anti-inflammatory effects were similar to or better than that of treatment with budesonide in asthmatic mice. Our data support the notion that IL-23 and associated Th17 responses contribute to the pathogenic process of bronchial asthma. Knockdown of IL-23 by RNAi effectively inhibits asthmatic inflammation, which is associated with mitigating the production of IL-17 and IL-4 in asthmatic mice.

Keywords: asthma; interleukin-23; mice; ovalbumin; RNA interference

Introduction

Bronchial asthma is a serious chronic illness with variable clinical symptoms. Because of increased environmental pollution, the incidence of bronchial asthma is increasing worldwide (Eder...