Curcumin attenuates allergic airway inflammation by regulation of CD4⁺CD25⁺ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice

Abstract

The present study aimed to determine the protective effects and the underlying mechanisms of curcumin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and curcumin (50 mg/kg, 100 mg/kg, 200 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright–Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Treg/Th17 cytokines were measured by enzyme-linked immunosorbent assay, Treg cells and Th17 cells were evaluated by flow cytometry (FCM). Our study demonstrated that curcumin inhibited OVA-induced increases in eosinophil count; interleukin (IL)-17A level were recovered in bronchoalveolar lavage fluid increased IL-10 level in bronchoalveolar lavage fluid. Histological studies demonstrated that curcumin substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry (FCM) studies demonstrated that curcumin remarkably inhibited Th17 cells and significantly increased Treg cells. The results in vivo show ovalbumin-induced significantly broke Treg/Th17 balance; curcumin treatments markedly attenuated the inflammatory in asthma model by regulating Treg/Th17 balance. Our findings support the possible use of curcumin as a therapeutic drug for patients with allergic asthma.

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.