The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis.
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PROVIDER: S-EPMC4807989 | BioStudies |
REPOSITORIES: biostudies
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Project description:Allergic rhinitis (AR) is a common allergic disease which is characterized by the promotion of Th2 differentiation of CD4+ T cells. However, the mechanisms underlying Th2 differentiation remain unclear. Non-coding RNAs play a critical role in Th2 differentiation, whereas few studies have revealed the interactions among long non-coding RNAs, circular RNAs, and microRNAs. In this study, the differential expressions of several circRNAs and lncRNAs were compared in nasal mucosa samples of AR patients and mice with experimentally induced AR as compared to healthy controls. The results showed that the highly expressed CircHIPK3 and LncGAS5 promoted Th2 differentiation of ovalbumin-induced CD4+ T cells and aggravated nasal symptoms of AR mice. We also found that CircHIPK3 and LncGAS5 induced the upregulation of Th2 cell-specific transcript factor GATA-3 via modulating their common target miR-495. Meanwhile, the intranasal administration of CircHIPK3 or LncGAS5 knockdown lentivirus decreased nasal symptoms of AR mice. In conclusion, our findings indicated that the interactions among CircHIPK3, LncGAS5, and miR-495 play a critical role in the regulation of Th2 differentiation in AR.
| S-EPMC7118158 | BioStudies
Project description:BACKGROUND:The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models. RESULTS:Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. CONCLUSION:Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.
| S-EPMC7542126 | BioStudies
Project description:To identify the effect of long noncoding RNA (lncRNA) FR215775 in regulating CD4+ T cells on murine models of allergic rhinitis (AR), the expression of lncRNA FR215775 in primary Th2 cells was detected through qRT-PCR. After knocking down the expression of lncRNA FR215775 via Sh-FR215775-Ads, Cell Counting Kit-8, cytometric bead array, and fluorescence-activated cell sorting were performed to determine its functions in vitro. Moreover, lncRNA FR215775-silencing or nonsilencing cells were injected intravenously into AR mice. Then, hematoxylin and eosin, Alcian blue-periodic acid Schiff, and toluidine blue staining were performed, and the levels of IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, IFN-<i>γ</i>, and TNF in the AR mice were also determined. We found that the expression of lncRNA FR215775 was specifically higher in the murine primary Th2 cells. After the knockdown of lncRNA FR215775, the proliferation of CD4+ T cells was inhibited, and the expressions of IL-4 and IL-5 in the cell culture supernatant were significantly decreased (<i>P</i> < 0.001), along with the percentage of Th2 cells (<i>P</i> < 0.05). The lncRNA FR215775-silencing AR group showed less serious allergic symptoms and a low level of ovalbumin-specific immunoglobulin E (<i>P</i> < 0.01). Meanwhile, the eosinophilia inflammation, goblet cell hyperplasia, and mast cell inflammation in the nasal mucosa all decreased, which indicated attenuated allergic inflammation in the lncRNA FR215775-silencing AR group. In addition, the Th2-related cytokines IL-4 and IL-5 were downregulated in the serum and nasal lavage fluid of this group (<i>P</i> < 0.01). In conclusion, lncRNA FR215775 may play a vital role in the function and differentiation of Th2 cells, which may encourage allergic inflammation. These results may provide significant insights into AR pathogenesis and offer new treatment targets for alleviating AR.
| S-EPMC9214652 | BioStudies
Project description:Purpose:Bisphenol A (BPA) is found in many plastic products and is thus a common environmental endocrine disruptor. Plastic-related health problems, including allergic diseases, are attracting increasing attention. However, few experimental studies have explored the effect of BPA on allergic rhinitis (AR). We explore whether BPA was directly related to the allergic inflammation induced by ovalbumin (OVA) in AR mice. Methods:We first constructed OVA-induced mouse model, and after BPA administration, we evaluated nasal symptoms and measured the serum OVA-specific IgE levels by ELISA. Th2 and Treg-related cytokines of nasal mucosa were measured by cytometric bead array. Th2 and Treg-specific transcription factor levels were assayed by PCR. The proportions of CD3+CD4+IL-4+Th2 and CD4+Helios+Foxp3+ T cells (Tregs) in spleen tissue were determined by flow cytometry. Results:Compared to OVA-only-induced mice, BPA addition increased nasal symptoms and serum OVA-specific IgE levels. OVA and BPA coexposure significantly increased IL-4 and IL-13 protein levels compared to those after OVA exposure alone. BPA plus OVA tended to decrease the IL-10 protein levels compared to those after OVA alone. Coexposure to OVA and BPA significantly increased the GATA-3-encoding mRNA level, and decreased the levels of mRNAs encoding Foxp3 and Helios, compared to those after OVA exposure alone. BPA increased the Th2 cell proportion, and decreased that of Tregs, compared to the levels with OVA alone. Conclusion:BPA exerted negative effects by exacerbating AR allergic symptoms, increasing serum OVA-specific IgE levels, and compromising Th2 and Treg responses.
| S-EPMC7495229 | BioStudies
Project description:BACKGROUND:Allergic rhinitis (AR) symptoms exhibit prominent 24-hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian-clock genes and AR symptoms at various time-points. METHODS:Based on the rhythmic secretion of corticosterone levels, we chose 2 time-points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian-clock gene period (Per) expressions. RESULTS:In the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T-helper 1 (Th1) cell counts and interferon-? levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)-4, -13, and -17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with Gata3 and Ror?t expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group. CONCLUSION:Our results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti-inflammatory effect on the circadian regulation of GATA3 and ROR?t levels in immune cells. This further demonstrates the neural-immune-endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR.
| S-EPMC7689743 | BioStudies
Project description:<h4>Background</h4>A formulation of black cumin (Nigella sativa L.), licorice (Glycyrrhiza glabra L.), anise (Pimpinella anisum L.) and tea (Camellia sinensis (L.) Kuntze) (denoted BLAB tea) is traditionally used to relief allergy reaction including allergic rhinitis. However, little is known about its underlining mechanism of anti-allergic effects.<h4>Methods</h4>To investigate the anti-allergenic mechanism of BLAB tea, we treated ovalbumin (OVA)-induced allergic rhinitis (AR) model of mice with BLAB tea, and elucidated its possible mechanism of action. Mice in the control group were treated with phosphate-buffered saline only. Subsequently, the infiltration of different inflammatory cells was measured. In addition, histopathological changes in the nasal mucosa, and the levels of allergen-specific cytokines and OVA-specific immunoglobulins were measured.<h4>Results</h4>The aqueous extract of BLAB significantly alleviated the nasal symptoms and reduced the accumulation of inflammatory cells in the nasal mucosa and nasal lavage fluid of AR model of mice.<h4>Conclusion</h4>The aqueous extract of BLAB induced the production of Th1 and Treg cytokines and inhibited the release of Th2 cytokines and histamine in nasal mucosa and serum of mice while decreasing the serum levels of OVA-specific IgE, IgG1, and IgG2a. These results suggest the potential of the aqueous extract of BLAB as a treatment option for allergic diseases.
| S-EPMC8424864 | BioStudies
Project description:Nasal hyperresponsiveness (NHR) is a characteristic feature of allergic rhinitis (AR); however, the pathogenesis of NHR is not fully understood. In this study, during the establishment of an experimental AR model using ovalbumin-immunized and -challenged mice, augmentation of the sneezing reaction in response to nonspecific proteins as well as a chemical stimulant was detected. Whether NHR is independent of mast cells and eosinophils was determined by using mast cell- and eosinophil-deficient mice. NHR was suppressed by treatment with anti-CD4 antibody, suggesting the pivotal contribution of CD4+ T cells. Furthermore, antigen challenge to mice to which in vitro-differentiated Th1, Th2, and Th17 cells but not naïve CD4+ T cells had been adoptively transferred led to the development of equivalent NHR. Since antigen-specific IgE and IgG were not produced in these mice and since antigen-specific IgE-transgenic mice did not develop NHR even upon antigen challenge, humoral immunity would be dispensable for NHR. CD4+ T cells play a crucial role in the pathogenesis of AR via induction of NHR, independent of IgE-, mast cell-, and eosinophil-mediated responses.
| S-EPMC4709066 | BioStudies
Project description:We investigated the mechanisms underlying the therapeutic effects of Yiqi Jiemin decoction (YJD), a traditional Chinese medicine (TCM), in the ovalbumin (OVA)-induced allergic rhinitis (AR) model in guinea pigs. YJD significantly decreased infiltration of mast cells and eosinophils into the nasal mucosa of AR model guinea pigs. YJD also increased expression of TGF-β in the nasal mucosa, restored the balance of Th1/Th2 immune cell responses, and decreased serum levels of various pro-inflammatory mediators, including histamine (HA), neuropeptide Y (NPY), acetylcholine (ACH), norepinephrine and immunoglobulin E (IgE). Metabolic analyses using liquid chromatography coupled with high-resolution mass spectrometry revealed that YJD improved cellular metabolism in AR model guinea pigs and increased serum levels of glycocholic acid while decreasing levels 1-palmitoyl lysophosphatidic acid. RNA-sequencing analysis identified <i>BPIFB2</i> as a potential diagnostic biomarker and therapeutic target for AR. Functional enrichment analyses showed that YJD significantly inhibited cytokine secretion pathways in AR model guinea pigs. These findings demonstrate that YJD protects against OVA-induced AR in guinea pigs by suppressing inflammation in the nasal mucosa, restoring Th1/Th2 balance, and improving cellular metabolism.
| S-EPMC8351690 | BioStudies
Project description:Objective and Design:Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory respiratory hypersensitivity characterized by elevated Th2 cytokines and infiltration of inflammatory cells to nasal tissues. BX471 is a small-molecule C-C chemokine receptor type 1 (CCR1) antagonist involved in suppression of inflammation via blocking of primary ligands. In this study, we examined the anti-inflammatory effect of BX471 on ovalbumin (OVA)-induced AR mice model. Materials and Methods:Levels of OVA-specific IgE and Th1 cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Nasal expression of proinflammatory mediators was assessed by real-time polymerase chain reaction (RT-qPCR). Nasal-cavity sections were stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to study eosinophil infiltration and goblet cell metaplasia. Relative protein levels of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB), Toll-like Receptor 4 (TLR4) and Toll-like-receptor 2 (TLR2) were assessed by Western Blot. Percentage of CD4+CD25+Foxp3+ T regulatory cells (Treg) was measured by flow cytometry. Results:Mice treated with BX471 showed significantly relieved sneezing and nasal-rubbing behaviors. The expression of nasal proinflammatory factors was significantly downregulated by BX471, and protein levels of tumor necrosis factor alpha (TNF- ?) and NF-kB were suppressed. Blockade of CCR1 ligands inhibited eosinophil recruitment in nasal cavity. In addition, Treg cells population were upregulated in BX471-treated mice. Conclusion:BX471 exerts anti-inflammatory effects in a mouse model of AR by inhibiting CCR1-mediated TNF-? production, which subsequently suppresses NF-kB activation in inflammatory cells, leading to a decrease in Th2 cytokines, IL-1?, VCAM-1, GM-CSF, RANTES, and MIP-1? expression levels, thus inhibiting eosinophil recruitment to nasal mucosa. In addition, BX-471 exhibits anti-allergic effect by increasing Treg cell population. Overall, BX471 represents a promising therapeutic strategy against AR.
| S-EPMC7398876 | BioStudies
Project description:<h4>Unlabelled</h4>T helper (Th)17 cells have been implicated in the development of allergic rhinitis (AR), but their response to specific immunotherapy (SIT) remains unclear. We investigated the impact of SIT on Th17 response and Th1/Th2 changes in AR patients. Blood samples from AR patients (n?=?20) who were monosensitized to house dust mite (HDM) were collected before the initiation of SIT (SIT-untreated) and after the end of 2-year SIT (SIT-treated) treatment. Twenty healthy volunteers were recruited as controls. In vitro HDM stimulation in peripheral blood mononuclear cells (PBMCs) was also performed. Expression levels of Th17 associated genes were determined in both PBMCs and plasma by PCR and ELISA, while Th17/Th1/Th2/IL10 producing cell proportions were evaluated in PBMCs by flow cytometry. The SIT effect was evaluated by assessing clinical symptoms. mRNA levels of Th17 specific genes (IL17 and RORC) were increased in SIT-untreated AR versus controls, and decreased following SIT treatment. SIT can change the production of Th17 associated genes (reduction of IL17, IL6, and IL23, but increase of IL27) in plasma from AR patients. Th2/Th1 ratio and proportions of Th17 cells were suppressed while IL10 producing CD4+ T cells were elevated after SIT. In vitro HDM challenge presents concordant patterns with in vivo findings: 1) increase of Th2 and Th17 response in AR patients; 2) suppression of IL10 producing CD4+ T cells in SIT-untreated AR but elevation in SIT-treated AR patients. Most importantly, a positive correlation between IL17 mRNA/protein levels and clinical symptom scores was observed. SIT significantly inhibits Th17 mediated inflammation in AR and IL17 may be a useful biomarker for both AR severity and SIT therapeutic effect.<h4>Trial registration</h4>Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000445774.
| S-EPMC3960160 | BioStudies