Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice
Graphical abstract
Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance.
Introduction
Asthma is a clinical diagnosis based on episodic symptoms and variable airway obstruction [1]. It has been generally recognized that the disease is also characterized by variable degrees of chronic inflammation and structural alterations in the airways [2]. Allergen-specific CD4+T cells are believed to play a pivotal role in the development of asthma [3]. Traditionally, it is thought that TH2-mediated chronic inflammation triggers and perpetuates a vicious circle of tissue injury–tissue repair culminating in remodeling. Th2 cells synthesize high levels of interleukin IL-4, IL-5, and IL-13, which lead to the production of allergen-specific immunoglobulin (Ig)E and the release of mediators from mast cells [4]. Th1 cells suppress Th2 immune responses by secreting interferon IFN-γ. IL-4 induces class switching in IgG1 and IgE, where as IFN-γ is involved in IgG2a class switching. Accordingly, estimation of IgE production and Th1/Th2 cytokine balance is an important tool in the evaluation of asthma [5]. Recently, regulatory T cells (Treg cells) and T-helper17 (Th17) cells have been described as two distinct subsets from Th1 and Th2 cells that play opposite roles in vivo [6]. Treg cells expressing the forkhead/winged helix transcription factor (Foxp3) have an anti-inflammatory role and maintain tolerance to self-components through direct contact with cells or by releasing anti-inflammatory cytokines such as IL-10 [7]. Th17 cells expressing retinoic acid receptor-related orphan receptor γt (RORγt) play crucial roles in the induction of autoimmune tissue injuries and inflammation by producing cytokines such as IL-17, tumor necrosis factor (TNF)-α, and IL-6. The balance between Th17 and Treg cell action may be important in the development/prevention of inflammatory and autoimmune diseases such as asthma [8].
Curcumin is an illustrious dietary ingredient of the Indian subcontinent [9]. Curcumin, in the form of the herbal powder, turmeric (given the name curry spice by the British), has been used for centuries as an anti-inflammatory remedy in Asian [10]. Turmeric has been studied extensively for its biological activities, predominantly as follows: antiinflammatory and antiarthritic [11], antioxidant [12], antimicrobial [13], anti-leishmanial [14], hepatoprotective [15], anticancer [16], vasodilator [17], hypolipidaemic [18], antiplatelet [19], hypoglycaemic [20], choleretic [21], antiulcer [22], antiscabies [23], wound healing [24], immunomodulatory [25], neuroprotective [26], antidepressant [27] and effective in Alzheimer's disease [28]. Curcumin has been used for the treatment of various inflammatory diseases in certain countries [29]. Curcumin has been reported to exert an anti-inflammatory effect, through desensitizing the nociceptor ion channel TRPA1 (As TRPA1 is specific to certain nociceptors, it is an attractive target for various therapeutic conditions such as pain, asthma, and cough) [30] and curcumin has been reported to exert an anti-asthma effect, through NF-κB inhibition [31]. The purposes of this study were to determine whether curcumin exerts an anti-inflammatory effect via regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice.
Section snippets
Chemicals and reagents
Curcumin (purity > 95%) was purchased from National Institutes for Food and Drug Control (Beijing, China). Dexamethasone was purchased from Xiansheng drug store (Nanjing, China). Ovalbumin (OVA), methacholine (Sigma Chemical Co., St Louis, MO), aluminum hydroxide (Pierce Biotechnology, Rockford, USA), and Wright–Giemsa staining (Nanjing Jiancheng Bioengineering institute, Nanjing, China). ELISA kits (R&D, Minneapolis, MN, USA).
Animals
Animal experiment was carried out in accordance with the Guidelines
Effect of curcumin on airway resistance (Raw)
Measurements of airway resistance (Raw), during methacholine-induced constriction are shown in (Fig. 2). The Raw value of the OVA-challenged group was significantly higher than that of the PBS control group (P < 0.05) when concentrations of 0.125–1.000 mg ml− 1 methacholine. OVA-sensitized and-challenged mice treated with curcumin, displayed a reduced mean Raw upon exposure to 0.5–1.0 mg ml− 1 compared with the response of the OVA-sensitized and -challenged group. Positive control mice given with
Discussion
Asthma, a chronic inflammatory disease of the airways, affects many individuals worldwide. The disease may cause severe morbidity, and even mortality if exacerbated. To date, a variety of drugs have been developed to treat asthma; these include steroids, leukotriene inhibitors, mast cell stabilizers, and β2 adrenergic agonists. Many nature products were commonly used to treat asthma, but the therapeutic efficacies and modes of action of such medicines are currently unclear. Here, using an
Acknowledgments
This work was supported by a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
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Chunhua Ma and Zhanqiang Ma contributed equally to this work.