A dichloromethane fraction of Triticum aestivum sprouts reduces allergic immune response through inhibiting Th2 differentiation in ovalbumin‑immunized mice

  • Authors:
    • Hyeon‑Hui Ki
    • Sung‑Woo Hwang
    • Ji‑Hyun Lee
    • Young‑Ho Kim
    • Dae‑Ki Kim
    • Young‑Mi Lee
  • View Affiliations

  • Published online on: July 15, 2017     https://doi.org/10.3892/mmr.2017.7020
  • Pages: 3535-3541
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Triticum aestivum sprouts are small shoots that germinate from seeds and are consumed as a dietary supplement. The present study aimed to determine whether a dichloromethane fraction isolated from Triticum aestivum sprouts (TDF) suppressed the allergic immune response in ovalbumin (OVA)‑sensitized mice. In vivo experiments were performed by administering TDF or vehicle to mice during the sensitization and this was immediately followed by an intradermal injection of OVA into the ears. Splenocytes isolated from OVA‑sensitized mice were pre‑treated with TDF and re‑challenged with OVA for ex vivo evaluation. Results demonstrated that TDF suppressed the inflammatory response in ear tissues and levels of total immunoglobulin (Ig)E and OVA‑specific IgE in serum. TDF inhibited the production of interleukin (IL)‑4 and expression of GATA‑binding protein‑3 (GATA‑3) transcription factor which regulates the differentiation of naïve T helper (Th) cells into Th2 cells in OVA‑stimulated splenocytes. TDF inhibited Th1‑associated cytokine interferon‑γ and IL‑12 production and downregulated the expression of Th1 specific transcription factor T‑box 21 in OVA‑stimulated splenocytes. Overall, these results indicated that TDF attenuates OVA‑induced allergic immune response by suppressing the production of Th2 specific cytokine IL‑4, through inhibiting transcription factor GATA‑3, and suggests that TDF may exhibit the potential to regulate the immune response in allergic diseases.

Introduction

Allergies are hypersensitivity reactions initiated in response to various environmental allergens. During sensitization to allergens through skin, and the respiratory and digestive tracts, B cells differentiate into immunoglobulin-producing cells and produce allergen-specific IgE, which binds to high-affinity receptor (FcεRI) on surfaces of mast cells in the connective or mucosal tissues (1). Subsequent exposure to the allergen activates mast cells through the cross-linking of FcεRI-IgE complexes, and activated mast cells then release amines with inflammatory vascular effects (e.g. histamine), leukotrienes derived from arachidonic acid, heparin, proteases, cytokines and chemokines. These factors promote allergic immune response by regulating the differentiations and activations of various immune cells and induce lymphocyte infiltration to the inflamed site (2). In addition, allergen-specific CD4+ Th2 cells are known to play important roles in the initiation and maintenance of allergic response (3). Cytokines (e.g. IL-4, IL-5, and IL-13) secreted by Th2 cells induce B cells to produce IgE and activate immune cells, including mast cells, basophils and eosinophils. On a macro scale, these responses cause mucus hypersecretion, epithelium fibrosis and are even associated with tissues damage (4).

Many medications used to treat allergic conditions, including antihistamines and corticosteroids, can cause side-effects. For example, long-term corticosteroid therapy may cause Cushing's syndrome, osteoporosis and adrenal insufficiency (57). Therefore, new therapeutic agents for the allergic diseases are today's need. Numerous authors have suggested that plant-derived drugs are intrinsically safer than synthetic drugs (8,9).

Triticum aestivum sprouts germinate from seed and contain large amounts of chlorophyll, minerals, enzymes, and other functional entities (10). Eosinophil accumulation and activation have been shown to play an important role in the pathogenesis of allergic inflammation and asthma (11,12). Studies have reported that in thalassemic patients with eosinophilia, Triticum aestivum sprouts reduced in the numbers of eosinophils in blood (13). We previously showed that a dichloromethane fraction isolated from Triticum aestivum sprouts (TDF) contains large amounts of sterols (e.g. β-sitosterol) and polyunsaturated fatty acids (e.g. α-linolenic acid) and glycolipids (14). Other studies have reported that β-sitosterol has potential anti-allergic effects (15,16), and increasing evidence indicates polyunsaturated fatty acids alleviate allergic diseases (17,18).

However, the effects of TDF on allergic immune response have not been elucidated. In the present study, we examined the anti-allergic activity and mechanism of action of TDF in an OVA-sensitized mouse model.

Materials and methods

Extraction and isolation of plant material

Triticum aestivum were supplied by the Korean National Institute of Crop Science and were germinated on sterile organic feat moss (at 20±2°C). The dichloromethane fraction was obtained from from Triticum aestivum sprouts (TDF) as previously described (14). Briefly, Triticum aestivum sprouts were cultivated for two weeks after germination, harvested, lyophilized and crushed to obtain a powder with a predetermined particle size. Frozen powder (30 g) was then extracted with methanol. And the extract was dissolved in 800 ml of water and partitioned sequentially with hexane, dichloromethane (CH2Cl2), ethyl acetate (EtOAc) and n-butanol. TDF was filtered through Whatman filter paper (grade no. 1, diameter: 15 cm) and concentrated under reduced pressure using a rotary evaporator (N-1000; EYELA, Tokyo, Japan).

In vivo experiments

Female BALB/c mice (6 weeks old) were purchased from Samtako (Osan, Korea), and acclimated in a pathogen-free facility for 2 weeks prior to experiments. Animals were kept in an air-conditioned room (22±2°C, 55±10% RH) and fed 5L79 rodent diet (Orient Bio, Seongnam, Korea) throughout the experimental period. The ovalbumin (OVA)-sensitized mouse model of this study was previously described by Park et al (19). After acclimation to the facility's environment, mice were divided into five groups (n=5 each): Group 1; 1% carboxymethyl cellulose (vehicle), group 2; OVA sensitization + vehicle, group 3; OVA sensitization + TDF 100 mg/kg, group 4; OVA sensitization + TDF 200 mg/kg, group 5; OVA sensitization + dexamethasone 0.5 mg/kg. On the first day, all mice were intraperitoneally (i.p.) sensitized with 20 µg OVA (grade V; Sigma-Aldrich, St. Louis, MO, USA) and 1 mg of aluminum hydroxide (Imject® A lum; Thermo Scientific, Cramlington, UK) dissolved in 100 µl of phosphate-buffered saline (PBS, pH 7.4); except mice in the group 1. Two weeks later, mice were administered a second i.p. injection of OVA and alum. To investigate in vivo effect of TDF on allergic immune response, OVA-sensitized mice were orally administered TDF or dexamethasone (p.o.) once daily for 13 days following the second OVA injection. All animal experiments were conducted after obtaining approval from the Institutional Animal Care and Use Committee (IACUC) at Chonbuk National University Laboratory Animal Center.

Ear swelling test

The ear swelling test was performed to analyze the allergic response with reference to the previous studies (20,21). Mice were injected subcutaneously with 20 µl of 0.1% (m/v) OVA solution dissolved in PBS into ear skin after the 13 days treatment period. Ear thicknesses of mice were measured using a thickness gauge (Mitutoyo, Tokyo, Japan) at 6 and 24 h after OVA injection.

Histological examination

Animals were sacrificed by cervical dislocation method under diethyl ether anesthesia. Ear tissues of animals were harvested at 24 h after final OVA challenge for histological examination. Tissues were fixed with 10% formalin and then embedded in paraffin. Tissue sections (4 µm) were obtained using a microtome for hematoxyin and eosin (H&E) staining, according to the previous report (22), and stained sections were examined under an optical microscope (CX21; Olympus, Tokyo, Japan).

Serum analysis of immunoglobulins

After sacrifice, blood was collected from abdominal inferior vena cava and centrifuged at 3,000 rpm for 10 min. Serum levels of total immunoglobulin (Ig)E and IgG1 were evaluated using commercial ELISA kits (BD Biosciences, San Jose, CA, USA), and the serum levels of OVA-specific IgE and OVA-specific IgG1 were measured using a detection kit obtained from Shibayagi (Gunma, Japan).

Preparation of splenocytes

Spleens were removed from OVA-sensitized mice and filtered using 100 µm cell strainers. Single-cell suspensions and Histopaque® 1119 (Sigma-Aldrich) were mixed and centrifuged at 1,600 rpm for 30 min to remove erythrocytes. The cell pellets so obtained were washed twice with PBS, and cultured in RPMI-1640 (HyClone Laboratories, Logan, UT, USA) supplemented with heat-inactivated 10% fetal bovine serum (FBS), 100 U/ml of penicillin and 100 µg/ml of streptomycin at 37°C in a humidified 5% CO2 incubator. Splenocytes were used for experiment after stabilization.

Reverse transcription polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR)

Splenocytes were treated with OVA and various concentrations of TDF for 24 h, and total RNA was extracted from splenocytes with TRIzol reagent (Invitrogen, Carlsbad, CA, USA). cDNA synthesis were performed using the SuperScript™ III First Synthesis system for RT-PCR kit (Invitrogen) and 1 µg of total RNA. Template of cDNA (50 ng) was amplified using 1X reaction buffer, 10 mM dNTP mixture, 5 units of Taq polymerase (GeNet Bio, Seoul, Korea) and RT-PCR primers. Amplified gene products were loaded into 1.5% agarose gel containing ethidium bromide, all gene expressions were normalized vs. GAPDH of each sample. qRT-PCR method was previously described (23). Primer sequences are summarized in Table I.

Table I.

Primer sequences and product size used for RT-PCR and qRT-PCR.

Table I.

Primer sequences and product size used for RT-PCR and qRT-PCR.

GeneForward primer (5′-3′)Reverse primer (5′-3′)Size (bp)
IFN-γ CTTCTTCAGCAACAGCAAGGCGAAAA CCCCCAGATACAACCCCGCAATCA456
IL-12 AACCTCACCTGTGACACGCC CAAGTCCATGTTTCTTTGCACC309
IL-4 GAGATCATCGGCATTTTGAAC CTTGGACTCATTCATGGTGCA267
IL-5 GAAAGAGACCTTGACACAGCTG GAACTCTTGCAGGTAATCCAGG277
IL-13 ATGAGTCTGCAGTATCCCG CCGTGGCAGACAGGAGTGTT194
GAPDH (RT-PCR) GCCAAGGTCATCCATGACAAC GTCCACCACCCTGTTGCTGTA498
T-bet ACTTTGAGTCCATGTACGCATCT AGGATACTGGTTGGATAGAAGAGGT113
GATA-3 TACCACCTATCCGCCCTATGT ACACACTCCCTGCCTTCTGT138
GAPDH (qRT-PCR) CATGGCCTTCCGTGTTC CCTGGTCCTCAGTGTAGC152

[i] IFN-γ, interferon-γ; IL, interleukin; T-bet, T-box 21; GATA-3, GATA binding protein-3; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Th1/Th2 cytokine assay

After preparation, splenocytes were incubated with various concentration of TDF in presence or absence of OVA (100 µg/ml) for 48 h. Th1 (IFN-γ, IL-12) and Th2 (IL-4, IL-5, IL-13) cytokines in cell culture supernatants were measured using the following ELISA kits: mouse IFN-γ, IL-12 and IL-4 kits were purchased from BioLegend (San Diego, CA, USA) and mouse IL-5 and IL-13 kits from eBioscience (San Diego, CA, USA).

Statistical analysis

Results are presented as means ± SEMs. The Student's t-test was carried out to verify the difference between the control and experimental groups in GraphPad Prism software (version 5.0). Statistical significance was accepted for p-values <0.05.

Results

Effect of TDF on allergic skin response in OVA-sensitized mice

Allergic inflammation can be elicited on sensitized subjects when exposure to a specific allergen (24). To investigate the inhibitory effect of TDF on cutaneous allergic response, mice were sensitized with OVA and administered TDF for 13 days, and then challenged with an s.c. injection of OVA into ears. Swelling responses were quantified by measuring ear thicknesses. As shown in Fig. 1A, ear thickness increases were significant compared to normal group at 6 and 24 h post-challenge. And TDF reduced these increases.

Histological analyses of ear tissues revealed marked increases in inflammatory cell infiltration into ear skin tissues after challenge in OVA-sensitized group. But these inflammatory cells infiltrations were inhibited dose-dependently by TDF (Fig. 1B). These results demonstrated that administration of TDF contributes to improving the allergic inflammatory response.

Effect of TDF on levels of serum immunoglobulins in OVA-sensitized mice

IgE production is considered the hallmark of allergic diseases, and thus, we investigated whether TDF can regulate the serum levels of immunoglobulins in OVA-sensitized mice. It has been reported that IL-4 secreted by Th2 cells promotes the productions of IgE and IgG4 in human and of IgE and IgG1 in mice (25). We found significant increases in the levels of serum total IgE and IgG1 in the OVA-sensitized group (Table II). Serum total IgE and IgG1 levels were about 6.6 and 2.8-fold greater, respectively, in the OVA-sensitized group than in the normal control group. Notably, serum levels of total IgE were significantly lower in the TDF 100 and 200 mg/kg groups than in the OVA-sensitized group, whereas total IgG1 levels were similar.

Table II.

The level of total IgE and IgG1 in serum of TDF treated OVA-sensitized mice.

Table II.

The level of total IgE and IgG1 in serum of TDF treated OVA-sensitized mice.

GroupTotal IgE (µg/ml)Total IgG1 (µg/ml)
Normal0.90±0.44 (15) 847.18±181.42 (35)
OVA-sensitized 6.02±1.03 (100) 2389.45±206.82 (100)
TDF 100 mg/kg 4.30±1.28 (71)a 2374.91±60.66 (99)
TDF 200 mg/kg 3.98±0.98 (66)a 2316.73±156.32 (97)
Dexa 4.12±1.28 (68)a 1594.45±222.29 (67)b

{ label (or @symbol) needed for fn[@id='tfn2-mmr-16-03-3535'] } Data are shown as mean ± SEMs.

a P<0.05

b P <0.01 vs. OVA-sensitized group.

To add, we obtained similar result after examination of OVA-specific IgE and IgG1 (Table III). OVA-specific IgE and IgG1 levels were obvious in the OVA-sensitized group but barely detectable in the normal control group. TDF treatment concentration-dependently suppressed serum OVA-specific IgE levels, but serum OVA-specific IgG1 levels remained unchanged in the TDF treated group.

Table III.

The level of OVA-specific IgE and IgG1 in serum of TDF treated OVA-sensitized mice.

Table III.

The level of OVA-specific IgE and IgG1 in serum of TDF treated OVA-sensitized mice.

GroupOVA-specific IgE (U/ml)OVA-specific IgG1(U/ml)
NormalNDND
OVA-sensitized 105.74±14.68 (100) 4741.24±1185.42 (100)
TDF 100 mg/kg 71.58±10.43 (68)a 4721.40±634.74 (100)
TDF 200 mg/kg 57.84±5.35 (55)b 4692.22±892.12 (99)
Dexa 63.48±10.22 (60)a 3432.45±793.27 (72)a

{ label (or @symbol) needed for fn[@id='tfn5-mmr-16-03-3535'] } Data are shown as mean ± SEMs.

a P<0.05

b P<0.01 vs. OVA-sensitized group. ND, Not detectable.

Effect of TDF on Th2-related cytokine level in splenocytes isolated from OVA-sensitized mice

By cellular interaction and cytokine secretion, Th cells play a key role in the class switching of B cells. Of the functional Th subsets, Th2 cells are important for enhancing allergic immune response. To determine the effect of TDF on Th2 response, we examined the mRNA and protein levels of Th2-related genes in splenocytes obtained from OVA-sensitized mice.

We observed increases of IL-4, IL-5 and IL-13 mRNA and protein levels in OVA-treated cells. However, TDF treatment at 100 µg/ml attenuated IL-4 mRNA expression and decreased IL-4 secretion (Fig. 2A and B). IL-5 and IL-13 mRNA (Fig. 2A) and protein levels tended (non-significantly) to be lower in TDF treated cells than in OVA-treated cells (Fig. 2C and D).

Effect of TDF on Th1 cytokine levels in splenocytes isolated from OVA-sensitized mice

Th1 and Th2 cells can inhibit each other by secreting cytokines, and naïve T cells differentiate into Th1 cells in the presence of IL-12, and Th1-derived cytokines (e.g. IFN-γ) are able to suppress Th2 differentiation (26). To investigate the effect of TDF on Th1 response, we examined Th1 response genes in splenocytes obtained from OVA-sensitized mice. Pre-treating splenocytes with TDF had no effect on the mRNA expressions of IFN-γ and IL-12 (Fig. 3A). However, IFN-γ and IL-12 secretions were significantly reduced by TDF, suggesting TDF reduced the levels of proteins involved in Th1 response without significantly changing mRNA levels (Fig. 3B and C).

Effect of TDF on the expressions of Th specific transcription factors in splenocytes isolated from OVA-sensitized mice

Due to the observed inhibition of Th1/Th2 related cytokine production by TDF in splenocyte culture, we further examined the expressions of transcription factors involved in skewing T cell polarization toward Th1 and Th2 cells (Fig. 4). As shown in Fig. 4A, TDF markedly inhibited the mRNA expression of T-bet, which plays a key role in Th1 differentiation. Likewise, the mRNA expression of the Th2 specific transcription factor GATA-3 was also inhibited dose-dependently by TDF (Fig. 4B).

Discussion

The prevalence of allergic diseases has increased in association with the western lifestyle in recent decades. Furthermore, it has been reported more than 25% of the populations of industrialized countries are under the influence of allergic diseases. The clinical manifestations of allergic diseases such as allergic rhinitis, asthma, atopic dermatitis, food allergy, allergic conjunctivitis and anaphylaxis can occur alone or in combination (2729). OVA-sensitized animal models are commonly used to mimic chronic allergic diseases such as asthma and atopic dermatitis in human (30,31). In the present study, we investigated the potential ameliorative role of TDF in allergic immune response using OVA-sensitized mouse model.

IgE mediated-mast cell degranulation induces an immediate hypersensitivity reaction to causes allergic inflammation. For example, edema is caused by the movement of immune cells on inflamed site, the expansion of blood vessels, and increased vascular permeability (32). In the present study, allergic cutaneous reaction was suppressed in TDF treated groups as compared with to the OVA-sensitized group. And this effect was comparable to that induced by dexamethasone (the positive control).

Allergic reactions are initiated by enhanced IgE production induced by activation of the Th2 pathway. Especially, antigen-specific IgE have a key role on mast cells. Mast cells which have FcεRI-bound IgE produce a diverse array of biologically active mediators when re-exposed to the antigens (33). We observed that TDF treatment significantly inhibited the total and OVA-specific IgE, when compared to the OVA-sensitized group. Our in vivo results suggest the observed suppression of allergic inflammation by TDF was due to IgE down-regulation.

We also investigated T cell regulation by TDF to explore further the natures of these IgE reductions. After an antigen encountered and bound by antigen presenting cells (APCs) in the body presents, the antigen to naive CD4+ T cells, which then differentiate into functionally distinct subsets as determined by the micro-environmental background.

Th2-biased immune responses commonly results in atopy, and is observed in blood and lung in the presence of asthmatic conditions, and thus, medications targeting Th cells are viewed as promising therapeutic strategies for the treatment of allergic diseases (34). Differentiation of naïve Th precursor cells into Th2 cells is characterized by the productions of Th2 cytokines (e.g. IL-4, IL-5 and IL-13). During Th2-development, Th2 signaling initiates activation of signal transducer and activator of transcription (STAT)-6 in the presence of IL-4, which is followed by the expressional up-regulation of GATA-3 (35). We observed TDF decreased the production of IL-4 and the mRNA expression of transcription factor GATA-3 induced by OVA stimulation in splenocyte, which result shows that TDF suppressed Th2 differentiation by inhibiting IL-4 production.

On the other hand, during the development of Th1 lineage cells, antigen stimulates APCs to secret Th1-promoting cytokines such as IL-12 and IFN-γ. In naïve Th precursor cells during T cell antigen receptor (TCR) engagement, IFN-γ activates STAT-1 and then downstream T-bet expressed in T cells. Furthermore, T-bet is known as a specific regulator for Th1 differentiation and to be related to IFN-γ production (36). Our results show that TDF inhibited the productions of the Th1 cytokines IFN-γ and IL-12 and decreased T-bet expression. Although Th1 and Th2 responses can block each other, this result confirmed that TDF does not participate in the induction of Th1 response and suggested that there are other mechanisms for inhibition of Th2 response. In addition, we examined the effect of TDF on other cell subsets such as regulatory T cells which have protective roles in the presence of excessive immune response. However, TDF was not found to have a significant effect on this subset (data not shown).

Triticum aestivum sprouts are known as contain flavonoids such as isoorientin, isoscoparin and luteolin as well as sterols and polyunsaturated fatty acids (37,38). These constituents have been reported to have the potential to ameliorate allergic diseases. For example, isoorientin was reported to suppress the release of histamine and leukotrienes in guinea pig lung mast cells activated by OVA (39), and luteolin was found to inhibit mast cell-mediated allergic inflammation and to attenuate immediate and late-phase asthmatic responses (40,41). Consistent to these studies, these factors could be evidences for beneficial effect of Triticum aestivum sprouts on allergic diseases.

In conclusion, our data reveal that TDF reduces OVA-induced allergic immune response by inhibiting Th2 differentiation mediated by the activation of GATA-3 and IL-4, and suggest that TDF could be useful for the treatment of allergic diseases. Further studies are required to elucidate the molecular targets associated with the TDF mediated inhibition of allergic immune response.

Acknowledgements

The present study was financially supported by grants from Wonkwang University (2017).

References

1 

Amin K: The role of mast cells in allergic inflammation. Respir Med. 106:9–14. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Larché M, Akdis CA and Valenta R: Immunological mechanisms of allergen-specific immunotherapy. Nat Rev immunol. 6:761–771. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Bosnjak B, Stelzmueller B, Erb KJ and Epstein MM: Treatment of allergic asthma: Modulation of Th2 cells and their responses. Respir Res. 12:1142011. View Article : Google Scholar : PubMed/NCBI

4 

Romagnani S: The role of lymphocytes in allergic disease. J Allergy Clin Immunol. 105:399–408. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Simons FE: Advances in H1-antihistamines. N Engl J Med. 351:2203–2217. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Buchman AL: Side effects of corticosteroid therapy. J Clin Gastroenterol. 33:289–294. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Warrington TP and Bostwick JM: Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 81:1361–1367. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Petry JJ and Hadley SK: Medicinal herbs: Answers and advice, part 1. Hosp Pract (1995). 36:57–60. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Balandrin MF, Klocke JA, Wurtele ES and Bollinger WH: Natural plant chemicals: Sources of industrial and medicinal materials. Science. 228:1154–1160. 1985. View Article : Google Scholar : PubMed/NCBI

10 

Mujoriya R and Bodla RB: A study on wheat grass and its Nutritional value. Food Sci Qual Manag. 2:2224–6088. 2011.

11 

Wardlaw AJ, Brightling C, Greesn R, Woltmann G and Pavord I: Eosinophils in asthma and other allergic diseases. Br Med Bull. 56:985–1003. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Till S, Dickason R, Huston D, Humbert M, Robinson D, Larché M, Durham S, Kay AB and Corrigan C: IL-5 secretion by allergen-stimulated CD4+ T cells in primary culture: Relationship to expression of allergic disease. J Allergy Clin Immunol. 99:563–569. 1997. View Article : Google Scholar : PubMed/NCBI

13 

Desai TR, Solanki JK, Buch Pankaj and Goyal RK: Triticum aestivum (Wheatgrass): An alternate treatment for the patients with Thalassemia. Orient Pharm Exp Med. 7:466–476. 2008. View Article : Google Scholar

14 

Luyen BT, Thao NP, Tai BH, Lim JY, Ki HH, Kim DK, Lee YM and Kim YH: Chemical constituents of Triticum aestivum and their effects on adipogenic differentiation of 3T3-L1 preadipocytes. Arch Pharm Res. 38:1011–1018. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Han NR, Kim HM and Jeong HJ: The potential anti-proliferative effect of β-sitosterol on human mast cell line-1 cells. Can J Physiol Pharmacol. 93:979–983. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Mahajan SG and Mehta AA: Suppression of ovalbumin-induced Th2-driven airway inflammation by β-sitosterol in a guinea pig model of asthma. Eur J Pharmacol. 650:458–464. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Arm JP, Boyce JA, Wang L, Chhay H, Zahid M, Patil V, Govindarajulu U, Ivester P, Weaver KL, Sergeant S, et al: Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics. Lipids Health Dis. 12:1412013. View Article : Google Scholar : PubMed/NCBI

18 

Barros R, Moreira A, Fonseca J, Delgado L, Castel-Branco MG, Haahtela T, Lopes C and Moreira P: Dietary intake of α-linolenic acid and low ratio of n-6:n-3 PUFA are associated with decreased exhaled NO and improved asthma control. Br J Nutr. 106:441–450. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Park EJ, Kim B, Eo H, Park K, Kim Y, Lee HJ, Son M, Chang YS, Cho SH, Kim S and Jin M: Control of IgE and selective TH1 and TH2 cytokines by PG102 isolated from Actinidia arguta. J Clin Immunol. 116:1151–1157. 2005. View Article : Google Scholar

20 

Schouten B, van Esch BC, Hofman GA, van den Elsen LW, Willemsen LE and Garssen J: Acute allergic skin reactions and intestinal contractility changes in mice orally sensitized against casein or whey. Int Arch Allergy Immunol. 147:125–134. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Hogenkamp A, Thijssen S, van Vlies N and Garssen J: Supplementing pregnant mice with a specific mixture of nondigestible oligosaccharides reduces symptoms of allergic asthma in male offspring. J Nutr. 145:640–646. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Poudel B, Yoon DS, Lee JH, Lee YM and Kim DK: Collagen I enhances functional activities of human monocyte-derived dendritic cells via discoidin domain receptor 2. Cell Immunol. 278:95–102. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Poudel B, Nepali S, Xin M, Ki HH, Kim YH, Kim DK and Lee YM: Flavonoids from Triticum aestivum inhibit adipogenesis in 3T3-L1 cells by upregulating the insig pathway. Mol Med Rep. 12:3139–3145. 2015.PubMed/NCBI

24 

Galli SJ, Tsai M and Piliponsky AM: The development of allergic inflammation. Nature. 454:445–454. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Aversa G, Punnonen J, Cocks BG, de Waal Malefyt R, Vega F Jr, Zurawski SM, Zurawski G and de Vries JE: An interleukin 4 (IL-4) mutant protein inhibit both IL-4 or IL-13-induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: Support for a common component shared by IL-4 and IL-13 receptors. J Exp Med. 178:2213–2218. 1993. View Article : Google Scholar : PubMed/NCBI

26 

Kidd P: Th1/Th2 balance: The hypothesis, its limitations and implications for health and disease. Altern Med Rev. 8:223–246. 2003.PubMed/NCBI

27 

Akdis CA: Allergy and hypersensitivity Mechanisms of allergic disease. Curr Opin Immunol. 18:718–726. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Yazdanbakhsh M, Kremsner PG and van Ree R: Allergy, parasites, and the hygiene hypothesis. Science. 296:490–494. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Holgate ST and Polosa R: Treatment strategies for allergy and asthma. Nat Rev Immunol. 8:218–230. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Nials AT and Uddin S: Mouse models of allergic asthma: Acute and chronic allergen challenge. Dis Models Mech. 1:213–220. 2008. View Article : Google Scholar

31 

Jin H, He R, Oyoshi M and Geha RS: Animal models of atopic dermatitis. J Invest Dermatol. 129:31–40. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Zgraggen S, Ochsenbein AM and Detmar M: An important role of blood and lymphatic vessels in inflammation and allergy. J Allergy (Cairo). 2013:6723812013.PubMed/NCBI

33 

Galli SJ and Tsai M: IgE and mast cells in allergic disease. Nat Med. 18:693–704. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Heijink IH and Van Oosterhout AJ: Strategies for targeting T-cells in allergic diseases and asthma. Pharmacol Ther. 112:489–500. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Chatila TA, Li N, Garcia-Lloret M, Kim HJ and Nel AE: T-cell effector pathways in allergic diseases: Aanscriptional mechanisms and therapeutic targets. J Allergy Clin Immunol. 121:812–823. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG and Glimcher LH: A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 100:655–669. 2000. View Article : Google Scholar : PubMed/NCBI

37 

Lee SH, Xin M, Luyen BT, Cha JY, Im JY, Kwon SU, Lim SW, Suh JW, Kim YH, Kim DK and Lee YM: Inhibitory effect of Triticum aestivum ethanol extract on lipid accumulation in 3T3-L1 preadipocytes. Yakhak Hoeji. 55:478–484. 2011.

38 

Luyen BT, Tai BH, Thao NP, Cha JY, Lee YM and Kim YH: A new phenolic component from Triticum aestivum sprouts and its effects on LPS-stimulated production of nitric oxide and TNF-α in RAW 264.7 cells. Phytother Res. 28:1064–1070. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Kim DS, Son EJ, Kim M, Heo YM, Nam JB, Ro JY and Woo SS: Antiallergic herbal composition from Scutellaria baicalensis and Phyllostachys edulis. Planta Med. 76:678–682. 2010. View Article : Google Scholar : PubMed/NCBI

40 

Kritas SK, Saggini A, Varvara G, Murmura G, Caraffa A, Antinolfi P, Toniato E, Pantalone A, Neri G, Frydas S, et al: Luteolin inhibits mast cell-mediated allergic inflammation. J Biol Regul Homeost Agents. 27:955–959. 2013.PubMed/NCBI

41 

Lee JY, Kim JM and Kim CJ: Flavones derived from nature attenuate the immediate and late-phase asthmatic responses to aerosolized-ovalbumin exposure in conscious guinea pigs. Inflamm Res. 63:53–60. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

September-2017
Volume 16 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ki HH, Hwang SW, Lee JH, Kim YH, Kim DK and Lee YM: A dichloromethane fraction of Triticum aestivum sprouts reduces allergic immune response through inhibiting Th2 differentiation in ovalbumin‑immunized mice. Mol Med Rep 16: 3535-3541, 2017
APA
Ki, H., Hwang, S., Lee, J., Kim, Y., Kim, D., & Lee, Y. (2017). A dichloromethane fraction of Triticum aestivum sprouts reduces allergic immune response through inhibiting Th2 differentiation in ovalbumin‑immunized mice. Molecular Medicine Reports, 16, 3535-3541. https://doi.org/10.3892/mmr.2017.7020
MLA
Ki, H., Hwang, S., Lee, J., Kim, Y., Kim, D., Lee, Y."A dichloromethane fraction of Triticum aestivum sprouts reduces allergic immune response through inhibiting Th2 differentiation in ovalbumin‑immunized mice". Molecular Medicine Reports 16.3 (2017): 3535-3541.
Chicago
Ki, H., Hwang, S., Lee, J., Kim, Y., Kim, D., Lee, Y."A dichloromethane fraction of Triticum aestivum sprouts reduces allergic immune response through inhibiting Th2 differentiation in ovalbumin‑immunized mice". Molecular Medicine Reports 16, no. 3 (2017): 3535-3541. https://doi.org/10.3892/mmr.2017.7020