AcCystatin, an immunoregulatory molecule from Angiostrongylus cantonensis, ameliorates the asthmatic response in an aluminium hydroxide/ovalbumin-induced rat model of asthma.
Epidemiological surveys have demonstrated that helminth infections are negatively related to atopic diseases, including asthma. Defining and characterising specific helminth molecules that have excellent immunomodulatory capacities as potential therapeutics for the treatment or prophylaxis of allergic manifestations are of great interest. AcCystatin, a cystatin protease inhibitor of Angiostrongylus cantonensis, is a homologue of other nematode cystatins with immunoregulatory properties. Here, we aim to determine the effects of AcCystatin on an ovalbumin/aluminium hydroxide (OVA/Al[OH]3)-induced rat model of asthma. Wistar rats were randomly divided into four groups, including a control group, an OVA/Al[OH]3-induced asthma group, a group receiving AcCystatin immunisation prior to OVA/Al[OH]3-induced asthma and a group receiving AcCystatin treatment after OVA/Al[OH]3-induced asthma. The numbers of eosinophils, basophils, neutrophils, lymphocytes and monocytes in the peripheral blood and of eosinophils in the bronchoalveolar lavage fluid (BALF) were counted for each animal. The expression levels of the cytokines interferon-γ, interleukin (IL) 4, IL-5, IL-6, IL-10, IL17A and tumour necrosis factor receptor-α in BALF, of OVA-specific immunoglobulin E in BALF and serum and of the chemokines eotaxin-1, eotaxin-2, eotaxin-3, MCP-1 and MCP-3 in lung tissue were measured. In addition, the degree of peribronchial and perivascular inflammation and the intensity of goblet cell metaplasia were qualitatively evaluated. The sensitised/challenged rats developed an extensive cell inflammatory response of the airways. AcCystatin administration significantly reduced the cellular infiltrate in the perivascular and peribronchial lung tissues and reduced both goblet mucous production and eosinophil infiltration. The rats that were treated with AcCystatin before or after sensitisation with OVA showed significant decreases in eotaxin-1, eotaxin-3 and MCP-1 expression in the lung tissue. The production of IL-4, IL-5, IL-6 and IL-17A and of OVA-specific IgE antibodies was also significantly reduced in AcCystatin-treated rats compared with untreated asthmatic rats. The AcCystatin treatment was associated with a significant increase in IL-10 levels. Our present findings provide the first demonstration that AcCystatin is an effective agent in the prevention and treatment of the airway inflammation associated with asthma.
Zhongshan School of Medicine, Sun Yat-sen University, 74 2nd Zhongshan Road, Guangzhou, 510080, China.
Pengyu
P
Ji
Huiling
H
Hu
Xiangyun
X
Yang
Xiaoxia
X
Wei
Chengcheng
C
Zhu
Jingchao
J
Liu
Yun
Y
Feng
Fan
F
Yang
Kamolnetr
K
Okanurak
Na
N
Li
Xin
X
Zeng
Huanqin
H
Zheng
Zhongdao
Z
Wu
Zhiyue
Z
Lv
D000536:Aluminum Hydroxide / Q000009:adverse effects; D017185:Angiostrongylus cantonensis / Q000737:chemistry*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015891:Cystatins / Q000008:administration & dosage* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology; D015801:Helminth Proteins / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010047:Ovalbumin / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar
D015891:Cystatins; D016207:Cytokines; D015801:Helminth Proteins; D007155:Immunologic Factors; D020381:Interleukin-17; D015848:Interleukin-5; D015850:Interleukin-6; D016753:Interleukin-10; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D007371:Interferon-gamma; D010047:Ovalbumin