Ovalbumin Allergy Research Articles

Impact of ovalbumin allergy on oral and gut microbiome dynamics in 6-week-old BALB/c mice.

The gut microbiota is known to have a significant impact on the development of food allergy, and several recent studies have suggested that both oral microbiota, which first come into contact with allergenic foods, may have a profound influence on the development of food allergy. In this study, we have established an ovalbumin-sensitive mice model by utilizing ovalbumin as a sensitizing agent. Subsequently, we performed a comprehensive analysis of the gut and oral microbiota in ovalbumin-sensitive mice and the control mice using full-length 16S rRNA sequencing analysis. Interestingly, both the gut and oral microbiota of ovalbumin-sensitized mice exhibited significant dysbiosis. The relative abundance of s__Lactobacillus_intestinalis in the gut microbiota of ovalbumin-sensitive mice exhibited a significant decrease, whereas the abundance of s__Agrobacterium_radiobacter and s__Acinetobacter_sp__CIP_56_2 displayed a significant increase. Furthermore, the relative abundance of s__unclassified_g__Staphylococcus, s__Streptococcus_hyointestinalis, and s__unclassified_g__Dechloromonas in the oral microbiota of ovalbumin-sensitive mice revealed a significant decrease. In contrast, the abundance of 63 other species, including s__Proteiniclasticum_ruminis, s__Guggenheimella_bovis, and s__Romboutsia_timonensis, demonstrated a significant increase. The random forest classifier achieved the best accuracy in predicting the outcome of food allergy using three gut and three oral biomarkers, with accuracies of 94.12 and 100%, respectively. Based on the predictions of the PICRUSt2 analysis, the only consistent finding observed across multiple samples from both the groups of mice was a significant up-regulation of the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway in the ovalbumin-sensitized mice. Our study demonstrates that ovalbumin-sensitized mice experience substantial alterations in both gut and oral microbial composition and structure, and specific strains identified in this study may serve as potential biomarkers for food allergy screening. Moreover, our findings highlight that the oral environment, under the same experimental conditions, exhibited greater precision in detecting a larger number of species. Additionally, it is worth noting that the NOD-like receptor signaling pathway plays a vital role in the pathogenesis of OVA (ovalbumin)-induced allergy. These findings will generate novel concepts and strategies in the realm of food allergy prevention and treatment.

DESCRIPTION OF CRP LEVELS IN ALLERGIC MICE AFTER KETEPENG LEAF INFUSA TREATMENT

Allergy is a hypersensitivity reaction that arises due to exposure to allergens. Allergens will bind to IgE attached to mast cells and cause these cells to release various chemicals in the blood. One of them is, histamine which causes most allergic reactions. Allergic reactions can cause inflammation or inflammation. Inflammatory stimulation will later stimulate the release of C-Reactive Protein (CRP). CRP is an inflammatory maker that is produced and synthesized in the liver. Ketepeng leaf infusion has the potential to stimulate an immune response because it contains chemical compounds, namely alkaloids, saponins, flavonoids, tannins, and anthracino. Flavonoids contained in this plant function to provide anti-inflammatory, antiallergic, antioxidant and antifungal effects. The purpose of this study was to determine the effectiveness of ketepeng leaves (Cassia alata L) by examining CRP (C-Reactive Protein) levels in Ovalbumin-allergic mice (Mus musculus). This type of research is Univariate, which is a method for making an overview of the state of the object being examined through data or sampling samples. The results of this study found that in group 2 after being given ovalbumin, CRP levels increased by 181.33 mg/L and in group 3, after being given ketepeng leaf infusion, CRP levels decreased by 48 mg/L. The conclusion of this study is that ketepeng leaf infusion can reduce CRP levels in mice with ovalbumin allergy and there is an effect of increasing CRP levels in mice given ovalbumin of 181.33 mg/L and a decrease in CRP levels after the treatment of ketepeng leaf infusion of 48 mg/L .

Synergistic effects of L-theanine and epigallocatechin gallate in alleviating ovalbumin allergy by regulating intestinal immunity through inhibition of mast cell degranulation.

Ovalbumin (OVA), a commonly consumed food protein, can cause severe allergies and intestinal immune disorders. L-Theanine (LTA) and epigallocatechin gallate (EGCG) regulate intestinal immunity. However, it is unclear whether an LTA and EGCG combined intervention can alleviate OVA allergy (OVA-A) by modulating intestinal-specific immunity, and it is unknown whether there is a synergistic effect between LTA and EGCG. Therefore, we treated BALB/c OVA-sensitized mice with LTA, EGCG, or a combination of both (LTA + EGCG) to investigate the effects of LTA and EGCG on intestinal-specific immunity regulation and underlying mechanisms. Female mice were intraperitoneally injected with OVA to establish OVA-sensitive mouse models. MLEO LTA + EGCG (20 mg kg-1 d-1 LTA + 80 mg kg-1 d-1 EGCG) and HLEO (30 mg kg-1 d-1 LTA + 120 mg kg-1 d-1 EGCG) exerted more beneficial effects on alleviating OVA-A (weight gain, allergy score, jejunum structure, mast cell [MC] degranulation, thymus and spleen indices) than LTA or EGCG alone (p < 0.01). Based on the alleviation of OVA-A by LTA + EGCG, we selected MLEO mice for 16S rDNA, flow cytometry, and western blot analyses. The 16S rDNA results showed that MLEO increased the abundance of Lactobacillaceae, Lachnospiraceae, and Ruminococcaceae, and decreased that of Helicobacteraceae (p < 0.01). The flow cytometry and western blotting results indicated that MLEO reduced the number of dendritic cells available to capture OVA, thereby lowering the Th2 immune response and decreasing the IL-4 and IL-13 levels. Meanwhile, the attenuation of the Th2 immune response inhibits the cross-linking of OVA and FcεRI, thus reducing MC degranulation and decreasing the serum HIS and mMCPT-1 levels through the FcεRI/Btk/PLCγ signaling pathway. LTA + EGCG also inhibits the Th2 immune response through the FcεRI/Lyn/Syk/PI3K/AKT signaling pathway and decreases the serum IL-4 and IL-13 levels. Notably, LTA + EGCG promotes the Treg and Th1 immune responses and inhibits the Th17 immune response, altering the levels of the corresponding cytokines. Therefore, LTA + EGCG can synergistically alleviate OVA-A by regulating intestinal immunity through MC degranulation inhibition.

Oral Intervention of Narirutin Ameliorates the Allergic Response of Ovalbumin Allergy.

A new intervention was investigated for the induction of oral tolerance (OT) of OVA using narirutin by in vivo and in vitro experiments combined with network pharmacology and structural analysis of molecular docking. Narirutin (and its metabolism naringenin) has effects on OT by affecting B cell function, DCs, and T cell response by prediction. It was verified that narirutin could affect B cell function of secreting antibodies, thereby reducing the ability of DCs to absorb antigens by affecting GATA3, CCR7, STAT5, and MHCII expression and regulating T cell response by suppressing Th2 and improving Treg cells in vivo. Molecular docking showed that steric hindrance effects may be the reason for weaker binding energy with targets of narirutin. However, this does not mean that it has no bioactivity, for it can inhibit mast cell degranulation. This finding is interesting because it offers the possibility of using natural compounds to promote oral tolerance.

Adjuvant effect of zymosan after pulmonary treatment in a mouse ovalbumin allergy model

ABSTRACTAn association has been observed between indoor mold contamination and lung allergy and asthma. This relationship is not fully understood. 1→3-β-Glucan is the major cell wall component of fungi and a good marker of fungi exposure. The objective was to evaluate the adjuvant effect of zymosan, a crude yeast cell wall preparation of 1→3-β-glucan, during ovalbumin (OVA) sensitization in an allergy model. BALB/c mice were sensitized by pharyngeal aspiration with saline, 50 μg of OVA, or OVA with 1, 10, 50, or 75 μg of zymosan on days 0, 7, and 14. One week after sensitization, each sensitized animal group was challenged with an aspiration dose of 50 μg of OVA once a week for 2 weeks. At 1 day after the last aspiration, bronchoalveolar lavage fluid and blood was collected, and markers of lung allergy and inflammation were assessed. An adjuvant effect of zymosan on OVA allergy during sensitization was observed as indicated by significant elevations in lung eosinophils, serum OVA-specific IgE, and lung IL-5 in the groups sensitized with zymosan and OVA. Pulmonary treatment with zymosan also amplified lung inflammation. Elevations were observed in lung neutrophils, TNF-α, and parameters of lung injury in the groups primed with both zymosan and OVA. In nearly all parameters, a non-linear dose–response relationship was observed in the groups primed with OVA and zymosan. The optimum adjuvant dose of zymosan was 10 μg. This study demonstrated an adjuvant effect of zymosan when exposures occurred during the sensitization phase in an OVA-induced allergy model in BALB/c mice.

Immune state in lung of BALB/c mice with ovalbumin allergy and the effects of fulvotomentoside on lungs of mice

To investigate immune state in lung of BALB/c mice with ovalbumin (OVA) allergy and the effects of fulvotomentoside (Ful) on lungs of the mice and provide some clues for the mechanism that patients with food allergies were prone to asthma and observe the effects of the treatment with traditional Chinese medicine. Ninety-six female BALB/c mice were randomly divided into 6 groups. Mice in group 1 and group 2 were sensitized intraperitoneally and challenged intragastrically with OVA and were exposed to phosphate buffer solution and OVA respectively by nebulized inhalation. Mice in group 3 and group 4 were treated with Ful, other processes were the same as the mice in group 1 and group 2, respectively. Mice in group 5 were not challenged intragastrically with OVA and other processes were the same as the mice in group 2. Group 6 was the control group. The number of total leukocytes and cell classification in bronchoalveolar lavage (BALF) were counted, and inflammatory characteristic of lung was scored by staining with hematoxylin and eosin. The protein expressions of transforming growth factor (TGF-β1), interleukin-6 (IL-6), interleukin-17 (IL-17A) in lung of the mice were detected by immunohistochemical method. The activation of neutrophils in lung was assayed by the level of myeloroxidase (MPO). There was no inflammatory cells infiltration in lung of the mice in group 1. Compared with group 6, numbers of total leukocytes and erythrocytes as well as the percentage of neutrophils and lymphocytes were increased in group 2. Inflammatory score and protein expressions of TGF-β1 [(75 437 ± 3 638) vs. (6 118 ± 1 978)], IL-6 [(121 650 ± 25 389) vs. (15 726 ± 9 360)], IL-17A [(252 105 ± 31 651)vs. (72 644 ± 12 285)] in lung were increased, too. Inflammatory score and TGF-β1 (11 054 ± 1 468), IL-6 (50 877 ± 11 744), IL-17A (137 864 ± 28 986) expressions in group 5 were lower than those in group 2. Eosinophils infiltration was significant in group 5. After the treatment with Ful, TGF-β1 expression did not change and IL-6, IL-17A expressions were decreased in lung of the mice that inhaled OVA. It was not enough for Ful to relieve the neutrophil aggregation and improve inflammatory reaction in lung. The expressions of TGF-β1, IL-6, IL-17A in lung of the mice with OVA allergy were increased markedly after they inhaled specific antigen, which caused serious inflammation that was induced by neutrophil infiltration in lung. Ful could decrease the expressions of IL-6, IL-17A to some extent, but it was not enough to improve pathologic state in lung.

청기거양탕(淸肌祛痒湯)의 RBL-2H3 비만세포와 OVA/alum 감작 생쥐의 알레르기 염증 반응 억제 효과

AbstractSuppressive Effect of CheongGiGeoYangTang on Allergic Inflammation of RBL-2H3 Mast Cells and OVA/alum-sensitized Mice Lee Hye Lim․Han Jae Kyung․Kim Yun HeeDepartment of Pediatrics, College of Oriental Medicine, Daejeon UniversityObjectivesCheongGiGeoYangTang has been used for anti-allergenic purpose. However there was no experimental study about its effect. Therefore, this study was designed to investi gate the anti-allergenic effect of CheongGiGeoYangTang. MethodsModifiability of RBL-2H3 mast cells' IL-4, IL-13 was analyzed b y qRT-PCR and ELISA. Also, the suppressive effect of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF- κB p65 transcription factors was observed by western blotting. OVA-specific IgE, IL-4 and IL-13 production in ovalbumin allergy model was examined as well.ResultsIt was showed that the RBL-2H3 mast cells treated with CheongGiGeoYangTang extract(CGGYT) was significantly suppressed mRNA expression, production of IL-4 an d IL-13, and prominently inhibited the expression of transcription factors including GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-κB p65 but not c-Jun. The administration of CGGYT was suppressed the amount of OVA-specific IgE, IL-4 and IL-13 in OVA/alum-sensitized mice.ConclusionsWe considered CGGYT would regulate the allergic inflammation as inhibition of IL-4 and IL-13 production in activated mast cells and Th2 cells.Key words : CheongGiGeoYangTang(淸肌祛痒湯), RBL-2H3 mast cell, OVA/alum-sensitized mice, IL-4, IL-13, Anti-allergic

Intradermal immunization with ovalbumin‐loaded poly‐ɛ‐caprolactone microparticles conferred protection in ovalbumin‐sensitized allergic mice

Although immunotherapy has been reported as the only treatment able to revert the T-helper type 2 (Th2) response, its administration has some disadvantages such as the requirement of multiple doses, possible side-effects provoked by conventional adjuvants and the risk of suffering an anaphylactic shock. For these reasons, drug-delivery systems appear to be a promising strategy due to its ability to (i) transport the allergens, (ii) protect them from degradation, (iii) decrease the number of administrations and (iv) act as immuno-adjuvants. The aim of this work was to evaluate the properties of poly-epsilon-caprolactone (PCL) microparticles as adjuvants in immunotherapy using ovalbumin (OVA) as an allergen model. For this purpose, the protection capacity of these microparticles (OVA PCL) against OVA allergy was studied in a murine model. The humoral and cellular-induced immune response generated by OVA encapsulated into PCL microparticles was studied by immunizing BALB/c mice intradermically. Also, OVA-sensitized mice were treated with OVA PCL and OVA adsorbed to aluminium hydroxide (OVA-Alum). Fifteen days after therapy, animals were challenged with OVA and different signs of anaphylactic shock were evaluated. One single shot by an intradermal route with OVA PCL resulted in a Th2-type immune response. In OVA-sensitized mice, treatment with OVA PCL elicited high OVA-specific IgG but low levels of IgE. Furthermore, OVA PCL mice group displayed lower levels of serum histamine and higher survival rate in comparison with the positive control group. The anaphylactic shock suffered by OVA PCL-treated mice was weaker than the one induced in the OVA-Alum group. Hence, the intradermal immunization with OVA PCL microparticles induced hyposensitization in OVA-allergic mice.

Inhibition of the IL-4/IL-13 receptor system prevents allergic sensitization without affecting established allergy in a mouse model for allergic asthma

Background: IL-4 and IL-13 are considered as key regulators for the development of atopic disease. Objective: This study addresses the therapeutic potential of an IL-4/IL-13 inhibitor on the basis of a mutated IL-4 variant (Q116D, Y119D) during allergic sensitization and in established disease in a murine asthma model with persistent airway pathologic condition. Methods: BALB/c mice were sensitized with ovalbumin intranasally. Mice were treated with the IL-4/IL-13 inhibitor during the sensitization phase or alternatively after ovalbumin allergy was established. Specific antibodies were measured, and histologic lung sections were examined for goblet cell metaplasia. In addition, bronchoalveolar lavages were performed and checked for airway eosinophilia, IL-5 levels, and the number of IL-4 secreting CD4+ T cells. Furthermore, airway responsiveness to inhaled methacholine was assessed. Results: The inhibition of the IL-4/IL-13 system during allergic sensitization resulted in a dose-dependent reduction of ovalbumin-specific IgEs and inhibition of airway eosinophilia together with decreased IL-5 levels and decreased numbers of IL-4 secreting CD4+ T cells. Moreover, goblet cell metaplasia and airway responsiveness to methacholine could be reduced significantly by the IL-4/IL-13 inhibitor. However, the inhibition of the IL-4/IL-13 system at various time points after allergy was established showed only little effect on all measured allergic parameters. Conclusion: Although the inhibition of the IL-4/IL-13 system can efficiently prevent the development of the allergic phenotype, these cytokines seem to play a minor role in established allergy. This is relevant for estimating the therapeutic effects of IL-4/IL-13 inhibitors in patients with allergic asthma. (J Allergy Clin Immunol 2003;111:1361-9.)

Modulation of the Th1/Th2 bias by an immunoglobulin histamine complex in the ovalbumin allergy mouse model

Vaccination with the antiallergic drug Histaglobin is used to treat a broad range of human allergic diseases including bronchial asthma, allergic rhinitis, and atopic dermatitis. In order to further elucidate its functional activity, Histaglobin was investigated in an in vivo mouse allergy model. Mice were sensitized with ovalbumin either prior to or after Histaglobin treatment, and its antiallergic potential was evaluated. Ovalbumin-sensitized mice exhibited increased serum levels of IL-4, tumor necrosis factor alpha (TNF-α), and an increase of total and ovalbumin-specific IgE; total and ovalbumin-specific IgG levels were also elevated. Subsequent administration (therapeutic treatment) of Histaglobin resulted in a decrease of total and specific serum IgE levels; total and specific IgG1 serum levels were reduced by more than 50% and 45%, respectively; the mice displayed a down-regulation of IL-4 and TNF-α serum levels and showed increased levels of IFN-γ and IgG2a. Mice pretreated with Histaglobin, prior to ovalbumin sensitization (prophylactic treatment), were found to be widely unresponsive to ovalbumin. They exhibited higher serum levels of IFN-γ and IgG2a (total and specific) compared to saline-treated control mice. The inhibitory effects were still observed 1 month post-immunization.Our data, indicating a Histaglobin-induced modulation of the Th1/Th2 balance in favour of Th1, correspond with the well-known antiallergic activity of Histaglobin observed in patients.

Lung eosinophils moonlight as antigen-presenting cells

Immune responses specific for exogenous antigens are initiated by professional antigen-presenting cells (APCs). Typified by the dendritic cell, APCs have several key characteristics that render them suitable for this role. First, APCs ‘survey’ their environs by engulfing particulate and fluid matter. Second, APCs traffic to T-cell-rich regions of the lymphoid tissue and display processed antigenic fragments of engulfed matter on their cell surface in conjunction with MHC class II. Finally, through binding of the MHC-class-II–antigen complex to the T-cell receptor (TCR), coupled with the additional expression of costimulatory molecules and directed secretion of regulatory cytokines, APCs activate and polarize cognate CD4+ T cells.Activated CD4+ T cells and other leukocytes are responsible for the effector phase of specific immunity. In tissues such as the skin, gastrointestinal system and lung, eosinophils are a predominant cellular feature of this response. In particular, eosinophils are thought to be key players in allergic disease and the resolution of parasitic infection, by virtue of their release of proinflammatory molecules (including cytokines) and granular proteins (such as peroxidase). However, as highlighted by a recent publication from the laboratories of Paul Foster, there is emerging evidence that eosinophils might participate also in the inductive phase of antigen-specific immunity.In their paper, J. MacKenzie et al. 1xEosinophils promote allergic disease of the lung by regulating CD4+ Th2 lymphocyte function. MacKenzie, J. et al. J. Immunol. 2001; 167: 3146–3155PubMedSee all References1 use a murine model of ovalbumin allergy in the lung to highlight the features of eosinophils that suggest they might act as APCs. In response to provocation of the airways of allergic mice with ovalbumin, eosinophils were found to accumulate in the blood and airways, take up and process ovalbumin and, subsequently, migrate through the pulmonary parenchyma to lung-associated lymph nodes. Furthermore, eosinophils purified from the pulmonary lumen of ovalbumin-challenged allergic mice expressed MHC class II and the costimulatory molecules CD80 and CD86. Under in vitro culture conditions, these eosinophils could induce the proliferation of sensitized CD4+ T cells and promote the secretion of T helper 2 (Th2) cytokines (although these were not proven to originate from the T cells themselves). Finally, the passive transfer of ovalbumin-loaded eosinophils to naive recipients was found to predispose to Th2-mediated allergic disease of the lung upon later ovalbumin challenge, suggesting that eosinophils can prime naive T cells.This publication, in conjunction with others cited therein, provides evidence of the capacity of eosinophils to act as APCs. Whether eosinophils are involved routinely in initiating new antigen-specific immunity or, merely, in amplifying existing responses remains to be determined. Interestingly, the current studies found no change in the levels of specific antibodies in response to the passive transfer of ovalbumin-loaded eosinophils and later ovalbumin challenge in naive mice, suggesting that, at least in terms of priming for antibody production, eosinophils are relatively poor APCs. However, in the context of allergy, eosinophils acting as APCs might play a crucial role in the exacerbation of existing Th2-polarized specific immunity by regulating CD4+ T-cell function within the pulmonary microenvironment.

Allergic reactions to measles (rubeola) vaccine in patients hypersensitive to egg protein

We evaluated two children with allergy to egg-white protein (ovalbumin) who had generalized urticaria, angioedema, and respiratory difficulty after immunization with live rubeola vaccine. In both patients, serum IgE reactive with ovalbumin-related antigens in the vaccine was demonstrated. Subsequent evaluation of 24 children with ovalbumin allergy revealed that those who had positive ovalbumin skin tests, but no clinical reaction to egg white, were skin test negative on prick and intradermal testing with measles vaccine and were safely immunized. They had no detectable IgE directed against the rubeola vaccine, although IgE directed at ovalbumin was present. Six patients who had severe allergic hypersensitivity reactions on exposure to ovalbumin had IgE antimeasles vaccine antibody and had positive reactions after intracutaneous or intradermal testing with the vaccine. These patients were safely immunized with increasing volumes (0.05 ml increments every 20 minutes) of measles vaccine to receive the full dose. These studies suggest that children with severe allergic hypersensitivity to egg white should be screened with an intracutaneous test prior to immunization with measles vaccine; however, children who have positive skin tests but no clinical reaction to ovalbumin exposure are at minimal risk for hypersensitivity reactions to measles immunization, as previously reported.