AcCystatin, an immunoregulatory molecule from Angiostrongylus cantonensis, ameliorates the asthmatic response in an aluminium hydroxide/ovalbumin-induced rat model of asthma

Abstract

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.

Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally-Induced Bronchial Asthma in Rats

“…Our results showed an efficient induction of bronchial asthma evidenced by significant and massive reductions in the respiratory functions TV and PEFR (table 1), which agreed with previous investigations in rats and mice [35,36,37]. Cytokines, particularly TNF-α, are involved in the initiation and progression of airway inflammation [38,39], with IL-5 particularly reported to have a central role in the initiation of eosinophilic airway inflammation [40], strongly agreeing with our results (table 2).…”

Myricetin Possesses Anthelmintic Activity and Attenuates Hepatic Fibrosis via Modulating TGFβ1 and Akt Signaling and Shifting Th1/Th2 Balance in Schistosoma japonicum-Infected Mice

“…Next, the melting curve was analyzed (95 • C for 15 s and 65 • C for 15 s.). The relative expression of each gene was calculated using the 2 − Ct method (18).…”

Helminth therapy for organic diseases?

“…The important role of IL-10 is supported by studies with a cystatin derived from the filarial helminth Acanthocheilonema vitae that suppresses both OVA and grass-pollen induced airways inflammation via induction of IL-10 producing macrophages 20;21 . Cystatin administration also decreases eotaxin-1, eotaxin-3 and MCP-1 expression in the lung tissues 22 . Another filarial product, the glycoprotein ES-62, protects from OVA-induced inflammation by reducing Th2 and Th17 responses and inducing Th1 responses 23 .…”