Against NF-κB/thymic stromal lymphopoietin signaling pathway, catechin alleviates the inflammation in allergic rhinitis

doi:10.1016/j.intimp.2018.06.011

International Immunopharmacology

Volume 61, August 2018, Pages 241-248

https://doi.org/10.1016/j.intimp.2018.06.011 Get rights and content

Highlights

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Catechin effectively remits the allergic symptom and Th2 inflammation in allergic rhinitis mice.
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Catechin reduces the expression of thymic stromal lymphopoietin(TSLP) and NF-κBp65 in nasal mucosa of allergic rhinitis mice.
•
Catechin inhibits the expression of TSLP and the activation of NF-κB signal pathway in human nasal epithelial cells(HNEpCs).

Abstract

Background

The prevalence of allergic rhinitis has risen sharply. Previous work has demonstrated the anti-inflammatory effect of catechin, including in models of allergic disease. However, the molecular mechanisms underlying this therapeutic effect remain unclear. Thymic stromal lymphopoietin(TSLP), as a molecule from epithelial cell, has been identified that plays a significant role in the development of allergic disease, and the production of TSLP is related to activation of the NF-κB signaling pathway. For that, we try to research the treatment of catechin for allergic rhinitis and found out possible mechanism under this effect, which was based on TSLP factor.

Materials and methods

Here, the anti-inflammatory effects of catechin were studied in an ovalbumin-induced allergic rhinitis murine model and a vitro experiments using poly(I:C)-stimulated human nasal epithelial cells(HNEpCs). The pharmacological effects of catechin in allergic rhinitis mice were assessed by observing the allergic symptoms, performing hematoxylin and eosin staining and Giemsa staining of the nasal tissues. Additionally, the TSLP expression in epithelial cells was tested by enzyme-linked immunosorbent assays, immunohistochemistry, and western blots. The serum levels of interleukin-5, interleukin-13, and ovalbumin-specific immunoglobulin-E were detected by enzyme-linked immunosorbent assays, and the balance between T helper type 1 and T helper type 2 cells was assessed by flow cytometry. The expression levels of phospho-NF-κBp65, IκBα, and NF-κBp65 proteins were further investigated by western blots or immunofluorescence.

Results

Our results reveal that catechin, in doses of 75, 150, or 300 mg/kg, remitted the allergic symptoms in mice with allergic rhinitis, like sneezing and nasal rubbing. Catechin could reduce the levels of interleukin-5, interleukin-13, and ovalbumin-specific immunoglobulin-E in the serum and restored the T helper type 2/T helper type 1 cell balance and also had anti-thymic stromal lymphopoietin effects. Moreover, as an upstream regulator of TSLP, the NF-κB signal pathway was also suppressed after catechin treatment, which was demonstrated by the observed decrease in phospho-NF-κBp65 and NF-κBp65 levels and the reduction of IκBα degradation and NF-κBp65 nuclear translocation.

Conclusions

Catechin effectively reduced the inflammation in allergic rhinitis. The underlying mechanism is that catechin inhibited the expression of TSLP in epithelial cells by influencing NF-κB/TSLP pathway.

Introduction

The prevalence of allergic diseases, including asthma, allergic rhinitis, and food allergies, has risen sharply in recent years. Allergic rhinitis as an inflammatory disease of the nasal mucosa induced by an immunoglobulin E-mediated reaction in allergen-sensitized individuals [1], is associated with numerous loci and candidate genes [2, 3]. Thymic stromal lymphopoietin(TSLP) has recently been reported to be one of the molecules closely related with the development of allergic disease [4, 5].

TSLP is an interleukin-7-like cytokine expressed mainly by epithelial cells [6]. Previous studies have provided compelling evidence that TSLP can activate dendritic cells to promote a T helper type 2 inflammatory response in allergic diseases [7, 8]; for example, TSLP can directly promote the T helper type 2 differentiation of naïve CD4⁺ T cells and the release of T helper type 2 inflammatory factors [9], such as interleukin-4, interleukin-5, and interleukin-13. Further work indicates that inflammation factors such as interleukin-1β, interleukin-13, and allergens can also induce the release of TSLP by stimulating the activation of NF-κB signaling [[10], [11], [12]]. Moreover, in vivo experiments revealed that the toll-like receptor agonists like poly(I:C), could induce epithelial cells to produce TSLP, and this was associated with the activation of NF-κB but not of IRF3 [13].

Catechin, the chemical structure of which is shown in Fig. 1, is a main effective component in green tea that has displayed anti-inflammation biological activity in both in vitro and vivo experiments [14, 15]. One study report that catechin could inhibit allergic inflammation in allergic keratitis and suppress NF-κB activation following lipopolysaccharide-induced inflammation in BV-2 microglial cells [16]. However, neither the ability of catechin to inhibit allergic rhinitis inflammation nor the associated molecular mechanisms underlying this therapeutic effect of catechin had yet been determined.

Here, we used an allergic rhinitis murine model induced by ovalbumin(OVA) to evaluate the TSLP and inflammation response factors during allergic rhinitis and to assess the effect of catechin treatment on this condition. Our study also stimulates human nasal epithelial cell line(HNEpCs) with TLR3 agonist poly(I:C) in vitro to determine the effect of catechin on the NF-κB signal and TSLP.

Section snippets

Animals

Female BALB/c mice (aged 6–8 weeks, weighing 18–22 g) were obtained from the Medical Experimental Animal Center of Guangdong Province (Guangdong, China), where mice were maintained under specific pathogen-free SPF) conditions. The experimental protocols were conducted under SPF conditions in the Laboratory Animal Center of Guangzhou University of Traditional Chinese Medicine, according to the guidelines approved by the Ethics Committee of Guangzhou University of Traditional Chinese Medicine.

Murine allergic rhinitis model and allergic symptoms

The

Catechin remits allergic symptoms and nasal inflammation in allergic rhinitis mice

To assess the effect of catechin administration on nasal symptoms of allergic rhinitis, the frequency of sneezing and nasal rubbing occurrences was counted for 10 min after ovalbumin sensitization. The mice were treated with catechin at doses of 75, 150, or 300 mg/kg before ovalbumin challenge. Catechin treatment clearly decreased the frequency of occurrences of sneezing (Fig. 3A) and nasal rubbing (Fig. 3B) as well as the level of ovalbumin-specific immunoglobulin-E in the serum of allergic

Discussion

Allergic rhinitis is an immediate type I allergic inflammatory response to inhaled allergens. Immune reactions participate in this condition include the recruitment of inflammatory cells to the nasal mucosa as well as the production and release of inflammatory mediators, such as thymic stromal lymphopoietin [18]. TSLP is a protein belonging to the cytokine family [19] and is produced mainly by non-hematopoietic cells, such as fibroblasts, epithelial cells [20]. These cells are located in

Conclusion

Our results revealed that catechin may be effective against allergic rhinitis inflammation. The likely mechanism for this is that catechin decreases the expression of TSLP in nasal epithelial cells by inhibiting the NF-κB/thymic stromal lymphopoietin signaling pathway.

Conflict of interest

The authors declare that they have no conflicts of interest to disclose.

Acknowledgements

This study was supported by the China National Natural Science Foundation (No.81373697) and National Natural Science Foundation of Guangdong (No. 2015A030313365).

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Against NF-κB/thymic stromal lymphopoietin signaling pathway, catechin alleviates the inflammation in allergic rhinitis

Highlights

Abstract

Background

Materials and methods

Results

Conclusions

Introduction

Section snippets

Animals

Murine allergic rhinitis model and allergic symptoms

Catechin remits allergic symptoms and nasal inflammation in allergic rhinitis mice

Discussion

Conclusion

Conflict of interest

Acknowledgements

Allergol. Int.

Front. Immunol.

Exp. Eye Res.

J. Allergy Clin. Immunol.

Int. J. Biochem. Cell Biol.

Int. Immunopharmacol.

J. Ethnopharmacol.

IgE and mast cells in allergic disease

Nat. Med.

Prevalence and risk factors of asthma, rhinitis, and eczema and their multimorbidity among young adults in Kuwait: a cross-sectional study

Biomed. Res. Int.

The topical treatment of allergic and vasomotor rhinitis: the role of beclomethasone dipropionate

Recenti Prog. Med.

Type 2 cytokine responses: regulating immunity to helminth parasites and allergic inflammation

Current pharmacology reports.

Thymic stromal lymphopoietin: a promising therapeutic target for allergic diseases

Int. Arch. Allergy Immunol.

Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma

Nat. Commun.

Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles

J. Exp. Med.

Thymic stromal lymphopoietin signaling in CD4(+) T cells is required for TH2 memory

J. Allergy Clin. Immunol.